
Class "^^ lL^ 
Book_'J:.<^ 
Copyright ^. 12 

COPWIGHT DEPOSIT. 



A GUIDE 

TO THE 

CLINICAL EXAMINATION 

OF 

THE BLOOD 

FOR DIAGNOSTIC PURPOSES 

EICHARD C/X]ABOT, M.D. 

^' WITH COLORED PLATES AND ENGRAVINGS 



ffourtb 1Rex>iset> BMtion 



NEW YOEK 
WILLIAM WOOD AND COMPANY 
MDCCCCI 




THE LIBRARY OF 

CONGRESS, 
Two Coptfcs Receiveo 

AUG. 30 1901 

COPVRtOHT ENTRY 

CLASS a. XXc N«. 
COPY 3. 



COPYRIGHT, 1901, 
By WILLIAM WOOD AND COMPANY. 



TO 



WILLIAM SIDNEY THAYEK, M.D., 

ASSOCIATE PROFESSOR OP MEDICINE IN JOHNS 
HOPKINS UNIVERSITY, 

IN GBATEFUL EECOGNITION OF THE STANDARD OF THOROUGH 
WORK ESTABLISHED BY HIM. 



PREFACE TO THE FOURTH EDITION. 



This book becomes with each succeeding edition more indebted 
to the labors of the internes of the Massachusetts General Hospital 
and less my book. Of the twelve thousand observations on which 
it is now based, less than three thousand represent my own work. 
The remainder I owe to the generosity of the visiting physicians of 
the hospital and to the zeal and skill of their internes. As the de- 
tails of the technique employed have been substantially the same 
throughout the whole body of data, they form a single group su- 
perior in bulk and in detail to any elsewhere recorded. Our twenty- 
eight hundred observations in one thousand cases of typhoid fever 
are an example of the wealth of statistical data on which the con- 
clusions of the book are based. 

The text has been almost entirely rewritten. The section on 
serum diagnosis has been abridged and the table of contents abbre- 
viated so that in spite of so many pages of new matter the book is 
not greatly increased in size. The most extensive changes are in 
the sections on pernicious anaemia, leukaemia, typhoid fever, and 
the diseases due to animal parasites. I have profited largely from 
the magnificent work of A. E. Taylor on leukaemia, the extensive 
observations on typhoid analyzed by Thayer, and Ewing's studies 
in malarial parasitology. 

190 Marlborough Street, Boston. 
August, 1901. 



TABLE OF CONTENTS. 



BOOK 1. 
Introduction. 

PAGE 

Scope and Value of Blood Examination, 3 

PAKT I. 

Methods of Clinical Examination of the Blood. 
CHAPTER I. 

I. Estimation of the Total Volume or Mass of Blood, . . . . 5 

II. Examination of the Fresh Blood, .7 

CHAPTER II. 

I. Counting the Corpuscles (Thoma-Zeiss Instruments), . . .13 

Counting the Red Corpuscles, 13 

Counting the White Corpuscles, 19 

Counting both Red and White Corpuscles with the Same Pipette, . 20 

II. Durham's Modified Haemocytometer, 23 

CHAPTER III. 

Other Methods of Examination, 27 

Oliver's Hcemocytometer, 27 

The Haematocrit, . . . .31 

Haemoglobin Estimation, 32 

I. Tallqvist's Haemometer, 32 

II. Dare's Haemoglobinometer, . . , . . . . .33 

III. Oliver's Haemoglobinometer, 35 

IV. V. Fleischl's Haemometer, .37 



viii TABLE OF CONTENTS. 

PAGE 

Estimating the Specific Gravity, 39 

Study of the Finer Structures of the Blood 41 

Bacteriological Examination, 47 

Other Methods of Examination, 49 



PAKT II. 
Physiology of the Blood. 
CHAPTER IV. 



Appearance of Feesh Normal Blood, 15 

I. Red Corpuscles, 51 

II. White Cells, 53 

III. Blood Plates, . . .53 

IV. Fibrin Network, 54 

Average Diameter of Red Cells, 55 

Normal Number of the Red Cells, 56 

Influence of Menstruation, Parturition, Lactation, . . . .57 

Influence of Vasomotor Changes, 57 

Influence of Nutrition, 57 

Influence of the Seasons, 58 

Influence of Fatigue, 58 

Influence of Age, . . . 58 

Normal Number of White Cells 59 

Normal Number of Blood Plates, . . . . . . .59 

MuUer's "Blood Dust," 60 

CHAPTER V. 

Finer Structure of the Blood, 61 

Appearances of Dried and Stained Specimens, 61 

Red Cells, 61 

White Corpuscles, 62 

Lymphocytes, . .62 

Transitional Cells, 63 

Polymorphonuclear Neutrophiles, 64 

Eosinophiles, 65 

Basophiles, 66 

Terminology, 66 

Normal Percentage of Each Variety, 67 

Myelocytes, . . 68 

Eosinophilic Myelocytes, 70 

Degenerated Leucocytes, . . 70 

Transitional Neutrophiles, 71 

Tiirck's "Stimulation Forms," ........ 71 



TABLE OF CONTENTS. 



ix 



PAET III. 
General Pathology of the Blood. 
CHAPTER VI. 

PAGE 

Unequal Distribution of the Blood — Polycythemia — Dilution 

AND Concentration of the Blood, 72 

1. Unequal Distribution, .72 

2. Local or Peripheral Polycythaemia. . . . . . .72 

(a) General Cyanosis, 73 

(b) Local Cyanosis, 73 

3. Temporary Serous Plethora, . . 74 

Polycythaemia, 74 

Concentration of the Blood, 75 

The Blood in High Altitudes, 78 

Phosphorus and CO Poisoning, ....... 79 

CHAPTER VII. 

Anemia and Hydremia, 80 

Anaemia, 80 

Pallor and Anaemia, 80 

" Tropical Anaemia, " 81 

Distinction between Primary and Secondary Anaemia, . . 81 
Secondary Anaemia, 83 

I. First Stage— Loss of Color, Weight, and Size, . ... 83 

II. Second Stage — Poikilocytosis and Degeneration, . . .83 

(a) Endoglobular Changes, 84 

(b) Crenation and Poikilocytosis, 84 

(c) Motility, • . .84 

{d) Oval Shape, 85 

(e) Changes in Staining Properties, 85 

(/) Lessened Diameter, . . . . . . . 86 

(g) Loss of Haemoglobin, 86 

III. Third Stage— Deglobularization, 87 

IV. Nucleated Red Corpuscles, 87 

(«) Normoblasts, .87 

(5) Megaloblasts, . . . . . . ' . . .88 

(c) Microblasts, .90 

(d) Atypical Forms, 90 

Summary, 91 

Hydraemia, 93 



X 



TABLE OF CONTENTS. 



CHAPTER VIII 

PAGE 

Leucocytosis— Lymphocytosis— EosiNOPHiLiA— Myelocytes, . . 94 

Definition of Leucocytosis, 94 

Physiological Leucocytoses, 97 

Digestion Leucocytosis, 97 

Diagnostic Value, 98 

Leucocytosis of the New -Born, 99 

Leucocytosis of Pregnancy, 100 

Leucocytosis after Parturition, 100 

Leucocytosis from Exercise, Massage, and Cold Baths, . . 100 

Terminal Leucocytosis, 103 

Pathological Leucocytoses, 104 

Post-hemorrhagic Leucocytosis, 104 

Inflammatory Leucocytosis, . . , 104 

Toxic Leucocytosis, 107 

Leucocytosis of Malignant Disease, 108 

Leucocytosis due to Therapeutic and Experimental Influences, . 109 
Cell Structure of the Leucocytes in Leucocytosis, . . .110 
Absence of Leucocytosis, . . . . . . . . .111 

Leucopenia, 112 

Lymphocytosis, „ 113 

Diagnostic Value, 115 

Eosinophilia, 115 

Diminution in Eosinophiles, 117 

Diagnostic and Prognostic Value, ...... 118 

Myelocytes, ,118 

CHAPTER IX. 

Genekal Pathology of the Blood as regards Hemoglobin, Fi- 
brin, LiPEMiA, Melanemia, and Hemorrhage, . . . 120 

Haemoglobin and the "Color Index," 120 

Fibrin, .121 

Lipgemia, . . 122 

Melansemia, . . . . 122 

Hemorrhage, . . . 123 

Changes in the Blood Resulting from Hemorrhage, . . , 123 

Blood Regeneration, 123 

Regeneration of Red Cells, 124 

Blood Crisis, 124 

Regeneration of White Cells, 125 

Importance for Surgery of Blood Counting after Hemorrhage, . 126 
Chronic Hemorrhage, 127 



TABLE OF CONTENTS. XI 



BOOK IL 
Special Pathology of the Blood. 

PAET I. 
Diseases of the Blood. 



CHAPTER I. 

PAGE 

The Primary Anemias, 131 

1. The Blood in Pernicious Anaemia, , . . . . . 131-151 

1. Volume and Oxygen Capacity, 131 

2. Gross Appearances, . . 131 

Red Cells and Haemoglobin, . . .... .132 

Quantitative Changes, 132 

White Cells, .135 

Quantitative Changes, 135 

Haemoglobin, 136 

Qualitative Changes, 137 

1. Red Corpuscles, 137 

(a) Increase in Diameter, 137 

(b) Deformities in Shape, 137 

(c) Staining Properties, . , 139 

2. Nucleated Red Corpuscles, 139 

3. White Corpuscles, 142 

The Blood in Remissions, 144 

Characteristics of Pernicious Anaemia, Summary, . . . 146 
Diagnostic Value of Pernicious Anaemia, 146 

1. Pernicious Anaemia and Chlorosis, ..... 146 

2. Pernicious Anaemia and Malignant Disease, . . . 147 

3. Pernicious Anaemia and other Secondary Anaemias, . . 148 

4. Pernicious Anaemia and Leukaemia, 149 

Prognostic Value of the Blood in Pernicious Anaemia, . , 149 

2. Fatal Anaemia with Hypoplastic Marrow, 152 

8. The Blood in Chlorosis, . . . . . . . . .153 

The Blood in Gross, 153^ 

Red Cells and Haemoglobin, . . . . . . .154 

Quantitative Changes, .154 

Qualitative Changes, 156 

Specific Gravity, 157 

White Cells, 157 

Quantitative Changes, . 157 

Qualitative Changes, 158 

Blood Regeneration in Chlorosis, ...... 158 

Chlorosis without Known Blood Changes, . . . .158 

Summary and Diagnostic Value, 159 



xii 



TABLE OF CONTENTS. 



CHAPTER 11. 

PAGE 

Leukemia, 160 

I. Myeloid Leukaemia, 161 

Red Cells, 161 

Quantitative Changes, 161 

Qualitative Changes, 162 

White Cells, , , . . .163 

Quantitative Changes, 163 

Qualitative Changes, 165 

1. Myelocytes, 165 

2. Polymorphonuclear Cells, 166 

3. Lymphocytes, 167 

4. Eosinophiles, 168 

5. Basophiles, 169 

6. Mitoses, 169 

7. Polymorphous Condition of the Blood, . . . 169 

8. Remissions, - . . 170 

II. Lymphaemia, 170 

Red Cells, 171 

White Cells, 171 

Quantitative Changes, 171 

Qualitative Changes, 172 

Summary of Blood Changes in Leukaemia, 175 

Differential Diagnosis of Leukasmic Blood, 175 

Effect of Intercurrent Infections in Leukaemia, . . . .177 

Hodgkin's Disease, 179 

The Blood, 180 

White Cells, 180 

Summary and Diagnostic Value, 184 

Effects of Splenectomy on the Blood, 184 

"Splenic AnaBmia," 185 

PART II. 
Acute Infectious Diseases. 
CHAPTER III. 

Influence of Fever on the Blood, 188 

Pneumonia, 189 

(«) Bacteriology of the Blood, 189 

(b) Coagulation and Fibrin, 190 

(c) Concentration of the Blood, 190 

(d) Specific Gravity, 190 

Red Cells, 190 

White Cells, . . . 191 

Quantitative Changes, 192 

Qualitative Changes, 193 



TABLE OF CONTENTS. xiii 

PAGE 

Diagnosis and PrognosiSj 195 

Broncho-Pneumonia, 197 

Typhoid Fever, ■ . .197 

Bacteriolog}^ of the Blood, 197 

Quantitative Changes, 198 

Red Cells, 198 

Haemoglobin, 200 

Leucocytes 200 

Complications, 203 

Qualitative Changes, 206 

Summary and Diagnostic Value, 207 

Prognosis. 209 

Diphtheria, . . . 210 

Red Corpuscles, : . . . 210 

Haemoglobin, 211 

White Corpuscles, 211 

Summary, 213 

CHAPTER IV. 

Acute Infectious Diseases {Continued). 

Scarlet Fever, 215 

Red Cells, 215 

White Cells, 215 

Summary, 216 

Diagnostic Value, 217 

Measles, Rotheln, and Mumps, . . . . . . . . 217 

Whooping-Cough, 218 

Small-pox (Variola), 219 

Chicken-pox, 221 

Acute Articular Rheumatism, 221 

Fibrin, Alkalinity, Red Cells, 221 

Qualitative Changes, Haemoglobin, Leucocytes, .... 223 

Summary and Diagnostic Value, 225 

Asiatic Cholera, 226 

Erysipelas, 227 

Tonsillitis (Follicular), 228 

Grippe, 229 

Septicaemia, 280 

Bacteriology of the Blood, 281 

Red Cells, 232 

Leucocytes, 236 

Summary and Diagnostic Value, . . ' 237 

Abscess, Iodine Reaction in, ......... 239 

Appendicitis, 240 

Leucocytosis, 243-246 

Differential Diagnosis, . . . 246 



xiv TABLE OF CONTENTS. 

PAGE 

Pus Tube, Pelvic Abscess, and Pelvic Peritonitis, .... 248 

Differential Diagnosis 249 

Otitis Media, . . .250 

Osteomyelitis, 251 

Other Abscesses, 251 

Diagnostic Value, 252 

Gonorrhoea, 253 

Yellow Fever, 253 

Typhus Fever, . . . . ' 254 

Malta Fever, 255 

Glanders, 255 

The Bubonic Plague, 256 

Actinomycosis, 256 

Epidemic Dropsy, 256 

Tetanus, 257 

Beri-beri, . . . / 258 

Relapsing Fever, . " 258 

CHAPTER V. 

Diseases Affecting the Seeous IMembranes, 259 

Serous Pleurisy, 259 

Summary and Diagnostic Value, 261 

Purulent Pleurisy (Empyema), 262 

Peritonitis, 264 

Diagnostic Value, 265 

Pericarditis (with Effusion), 265 

Diagnostic Value, 266 

Meningitis, 266 

Epidemic Cerebro-Spinal Meningitis, 267 

Diagnostic Value, 268 



PART III. 
Chronic Infectious Diseases. 



CHAPTER VI. 

Tuberculosis, Syphilis, and Leprosy, 269 

Tuberculosis, . . .269 

Red Corpuscles and Haemoglobin, 269 

(a) Quantitative Changes, 269 

(b) Qualitative Changes, 270 

Leucocytes, 271 

Changes in Phthisis, 271 

Changes in Bone Tuberculosis, 275 

Changes in Acute Miliary Tuberculosis, .... 277 



TABLE OF CONTENTS. XV 

PAGE 

Changes in Tuberculous Peritonitis, 280 

Changes in Tuberculous Meningitis, 383 

Changes in Tuberculous Pericarditis, . . . . . 385 

Changes in Tuberculous Pleurisy, 385 

Changes in Glandular Tuberculosis, 385 

Changes in Genito -Urinary Tuberculosis, .... 386 

Syphilis, 386 

Changes in Red Cells and Haemoglobin, 386 

Justus' Reaction, 388 

Changes in White Cells, ........ 389 

Diagnostic Value, 390 

Leprosy, 391 



PART IV. 
Diseases of Special Organs. 
CHAPTER VII. 



Diseases op the Digestive Appakatus, 393 

Diseases of the Stomach, . 393 

Anorexia Nervosa, . . . . • " 393 

Gastric Ulcer, 393 

Acute Gastritis and Dyspepsia, . . . . « . . 398 

Chronic Gastritis, 399 

Hyperacidity and Hypersecretion, 300 

Dilated Stomach, ^ . . .300 

Corrosive Gastritis, . . 301 

Diseases of the Intestine, . 301 

Influence of Saline Cathartics on the Blood, .... 301 

Acute Enteritis, 301 

Chronic Diarrhoea, 303 

Intestinal Obstruction, 304 

Diseases of the Liver, 304 

Catarrhal Jaundice, 304 

Qualitative Changes of Red Cells, 306 

Summary and Diagnostic Value, 306 

Cirrhosis of the Liver, 307 

1. Ordinary (Atrophic) Cirrhosis without Jaundice, . . 307 

Qualitative Changes, 307 

Haemoglobin, 309 

White Cells, 309 

3. Hypertrophic Cirrhosis with Jaundice, .... 310 
Red Cells and Haemoglobin, ...... 310 

White Cells 310 

Diagnostic Value, . . . 311 



xvi TABLE OF CONTENTS. 

PAGE 

Hydatid Cyst of the Liver, .... .... 311 

Acute Yellow Atrophy of the Liver, 311 

Phosphorus Poisoning, 311 

Cholaemia, 312 

Gall Stones .312 

Cholangitis 314 

Abscess of the Liver, 315 

Cancer of the Liver, 315 

Gumma of the Liver, 315 

Hemorrhagic Pancreatitis, 315 

Diseases Affecting the Heart, 316 

Pericarditis 316 

Endocarditis, 316 

Ulcerative Endocarditis, 316 

Red Cells, . 316 

White Cells, 317 

Diagnostic Value, 319 

Myocarditis, 320 

Valvular Heart Disease 320 

Red Cells, 321 

White Cells, 322 

Congenital Heart Disease, . . ^ 323 

Aneurism, . . ' 326 

Diseases of the Kidneys, 327 

Acute Nephritis 327 

Red Cells and Haemoglobin, 327 

White Cells, 329 

Chronic Diffuse and Chronic Parenchymatous Nephritis, . . 329 

Red Cells and Haemoglobin, 329 

White Cells, 331 

Chronic Interstitial Nephritis, 333 

Pyelo -nephritis, 335 

Stone in the Kidney, . 335 

Diagnostic Value, .... .... 337 

Floating Kidney, 337 

Pyonephrosis, . . . . . .. . . . . 337 

Diseases of the Lungs, 337 

Bronchitis, . . . 337 

Acute Bronchitis, 338 

Chronic Bronchitis, . . . , . . . . 339 

Emphysema and Asthma, ........ 340 

Syphilis of the Lung, 342 



TABLE OF CONTENTS. 



xvii 



PAET V. 

Diseases of the Nervous System, Constitutional Diseases, 

AND HeMOKKHAGIC DISEASES. 

CHAPTER VIII. 

PAGE 

Diseases op the Nervous System, . ... . . . . 343 

Neuritis, . . . . ... . . . . .343 

Diseases of the Brain, . . . 344 

Chorea and Tetany, . . . . ... . . . 346 

Diseases of the Spinal Cord, 346 

General Paralysis of the Insane, 346 

Hysteria and Neurasthenia : Hypochondriasis, 347 

Mental Diseases, 348 

Constitutional Diseases, . i 349 

Obesity, .349 

Diabetes, 349 

Red Cells, . . . 350 

White Cells, 350 

Gout, 351 

Myxoedema, 351 

Cretinism, 353 

Graves' Disease, 353 

Addison's Disease, 354 

Osteomalacia, 355 

Rickets, 356 

Red Cells, 356 

White Cells, 356 

Qualitative Changes, ...... . . . ■ . 357 

CHAPTER IX. 

Blood Destruction and Hemorrhagic Diseases, .... 358 

Purpura Haemorrhagica, 385 

Scurvy and Barlow's Disease, . • • • • • • 359 

Haemophilia, . . . . ^ .... . . 359 

Blood Destruction, ... 360 

Haemoglobinsemia in Infectious Diseases, 360 

Paroxj^smal Haemoglobinaemia, 360 

Blood Examination, . 361 

Burns, Snake Poison, etc., 361 

Poisons, Chlorate of Potash, Antipyretics, etc., .... 361 

Illuminating Gas, 364 

Tansy Poisoning, 365 

Corrosive Poisoning, . . 365 



xviii TABLE OF CONTENTS. 

PAGE 

Opium Poisoning, 365 

Ptomain Poisoning, 366 

Acute Alcoholism, 366 

Plumbism, 367 

Sunstroke and Heat Exhaustion, 368 



PART VI. 

Malignant Disease, Blood Parasites, and Intestinal 
Parasites. 



CHAPTER X. 

Malignant Disease, 370 

The Blood as a Whole, . . , 370 

Cancer, 370 

Red Cells, 370 

Quantitative Changes, 371 

Hsemoglobin, 373 

Regeneration of Blood after Operations on Cancerous 

Growths, 373 

Qualitative Changes in Red Cells, 375 

White Cells, . .377 

Quantitative Changes, 377 

Influence of Position and Size of Tumor, .... 377 

Influence of Individual Constitution, 378 

In Cancer of the Breast, 379 

In Cancer of the Stomach, 380 

Digestive Leucocytosis in Gastric Cancer, . . . . 382 

Effect of Metastases in Gastric Cancer, .... 383 

In Cancer of the Gullet, 384 

In Cancer of the Liver, 385 

In Cancer of the Intestine, 386 

In Cancer of Omentum and Abdominal Organs Generally, . 387 

In Cancer of the Kidney, 388 

In Cancer of the Uterus, 389 

In Cancer of other Organs, ....... 390 

Qualitative Changes in the Leucocytes, 391 

Sarcoma, 394 

Red Cells, 394 

HjBmoglobin, 396 

White Cells, 396 

Qualitative Changes of Leucocytes, 389 

Summary, 399 

Diagnostic Value, . . , 400 



TABLE OF CONTENTS. xix 
CHAPTER XI. 

PAGE 

Blood Parasites, 403 

Examination for the Plasmodium Malariae and Its Products, . . 402 

Time for Examination, . . 402 

Method of Examination, 402 

The Malarial Organism, . 404 

Recognition of Hyaline Forms, 404 

Pigmented Forms, 405 

Segmentation, 406 

Comparison of Tertian and ^stivo-Autumnal Rings. . . 407 

Crescentic Bodies, 408 

Flagellate Bodies, 409 

Pigmented Leucocytes, 410 

Staining the Malarial Organism, 411 

Other Changes in the Blood, 414 

Red Corpuscles, 414 

Hcemoglobin, 415 

White Cells, 415 

Malarial Hsemoglobinaemia, 416 

Typhoid Fever and Malaria, 416 

CHAPTER XII. 

Diseases due to Animal Parasites, 417 

Filaria Sanguinis Hominis, 417 

Spirochaete of Relapsing Fever, . . . . . . . . 422 

Technique of Examination, 422 

Distomum Haematobium, 426 

Anaemia due to Intestinal Parasites, 426 

Bothriocephalus Anaemia, . 426 

Ankylostomiasis (Uncinariasis), 428 

The Blood in Gross, 429 

Quantitative Changes 480 

Red Corpuscles, . 430 

White Corpuscles, 431 

Haemoglobin, 431 

Qualitative Changes, 431 

Red Corpuscles, 431 

Normoblasts and JMegaloblasts, 431 

White Corpuscles, . . • 432 

Trichinosis, 434 

Summary and Diagnostic Value, ....... 440 

Other Intestinal Worms, 440 

CHAPTER XIII. 

Diseases of the Skin, 442 

Dermatitis Herpetiformis, 442 



XX 



TABLE OF CONTENTS. 



PAGE 

Herpes Tonsurans, . . „ 443 

Chronic Eczema, 443 

Scleroderma, 443 

Psoriasis, 443 

Pemphigus, 444 

Lupus, 444 

CHAPTER XIV. 

The Blood in Infancy, 445 

General Characteristics, 445 

The Anaemias of Infancy, 447 

Classification, 448 

Secondary Anaemias, 448 

Qualitative Changes, 449 

" Anaemia Infantum Pseudoleukaemica," 450 

Importance of the Term, 452 

Pernicious Anaemia in Infancy, 454 

Polymorphous Condition, 456 

Leukaemia in Infancy, 456 

PAET VII. 

EXAMIXATIOX OF THE SeRUM. 

CHAPTER XV. 

The Clump Reaction, 458 

General Description, 458 

Technique, 460 

The Body Fluids Used, 460 

Use of the Whole Blood— Fluid, . 460 

Use of the Whole Blood — Dried, . 461 

Use of the Fluid Serum, 461 

The Cultures of Typhoid Bacilli to be Used, .... 462 

The Use of Suspensions instead of Cultures, .... 463 

The Use of Attenuated Cultures, . . . . . . . 463 

Dilution and the Time Limit, 463 

The Microscopical Examination, 464 

General Statistics, 464 

How Early does the Reaction Appear? 464 

■ How Late does the Reaction Last? 465 

The Intensity of the Reaction, . , . . . . . 465 

Control Cases, 465 

Summary of Clinical Evidence, . . . . . . . 466 



TABLE OF CONTENTS. Xxi 

PAGE 

Sero-Diagnosis of Other Diseases, 466 

Cholera 466 

Malta Fever, 466 

The Bubonic Plague, .467 

Appendix A. Neusser's Perinuclear Basophilic Granules, . . . 469 
Appendix B. Statistics in 121 Cases of Pernicious Anaemia, . . . 470 

Appendix C. Red Cells in Chlorosis, 483 

Appendix D. Leucocytes in Trichinosis, 484 

Bibliography, 487 

Index, 491 



BOOK I. 



INTRODUCTION. 



SCOPE AND VALUE OF BLOOD EXAMINATION. 

HEMATOLOGY has now established for itself a definite field of 
usefulness in the practice of medicine. It has solved some prob- 
lems where least was hoped from it, and given us disappointingly 
little help where great expectations had been aroused. We might 
have expected from it some light on the nature of rheumatism, fu- 
runculosis, uraemia, diabetes, but none has come. 

On the other hand, who could have hoped that it would help us 
in the diagnosis of central pneumonia, of deep-seated suppurations, 
and of trichinosis, or in the prognosis of relapsing fever or of pneu- 
monia? 

There are probably not more than five or six diseases in which 
the blood examination gives us the diagnosis ready-made, but there 
is a very considerable number of conditions in which the blood ex- 
amination will help us to make it. Not pathognomonic signs, but 
links in a chain of evidence are what we are to expect from blood 
examination. Very often the simple discovery that the blood is 
normal may be a fact of the greatest value in diagnosis. 

On the whole it seems to me that the examination of the blood 
gives evidence similar in kind and not much inferior in value to 
that obtained by examination of the urine. Both methods of ex- 
amination give us (<x) a ready-made diagnosis in a few diseases ; (b) 
side lights on a good many obscure conditions; and (c) the fre- 
quently great assistance of a negative report. In certain wards of 
the Massachusetts General Hospital it has been for some years the 
rule to examine the blood of every patient as a matter of routine 
at the time of entrance. In a small proportion of cases this gave 
negative evidence only; in a much larger proportion it materially 
assisted in the making of a diagnosis. 

Improvements in technique have lessened the labor and increased 
the accuracy of blood examination. The most important facts 



4 



INTRODUCTION. 



about the blood of nearly every case can be obtained by a practised 
observer in fifteen minutes. 

The blood is the only tissue that we can study easily during the 
life of the patient. Its relations to all other tissues are such that 
ib is typical of them all in a way that no other tissue is, acting on 
all and being acted on by all. As yet we have studied chiefly its 
morphology, and from that single aspect obtained most of the clini- 
cally valuable information which we possess about it. Bat the 
field of the blood chemistry is in many respects even more promis- 
ing at the present time, and there seems reason to believe that the 
study of the blood is still in its infancy and will take a higher place 
in the future as an aid to diagnosis, prognosis, and treatment. 

Like all methods of physical examination it has especial useful- 
ness when we cannot communicate with a patient, either by reason of 
his unconsciousness, stupidity, or insanity, or because he speaks no 
widely used language. In such cases the detection of marked anse- 
mia^ leucocytosis, eosinophilia, a typhoid serum reaction, or a mal- 
arial organism may be of great assistance. Malingering is made 
more difficult by it, and in the differentiation of organic from func- 
tional disease it is often very helpful. There is no febrile disease 
on which it may not throw light. 

The evidence for these and many other aids furnished by the 
blood examination in clinical work is given in the later chaj^ters of 
this work. 



PART I. 



METHODS OF CLINICAL EXAMINATION OF 
THE BLOOD. 



CHAPTER I. 

CoxFixixG ourselves lo the cliuically available processes by 
which we can gain information of diagnostic or prognostic value, 
blood examination at the present time embraces the following proc- 
esses. 

1. Estimation of the total volume of the blood and of its oxygen 
capacity. 

2. Examination of the fresh blood (with or without a warm 
stage). 

3. Counting the red and the white corpuscles. 

4. Estimation of the amount of coloring matter. 

5. Examination of dried and stained specimens. 

6. Bacteriological examination of the blood. 

7. Examination of the serum. ^ 

8. Estimation of the coagulation time. 
Less important are : 

9. Estimation of volume of corpuscles and of plasma in a given 
quantity of blood. 

10. Estimation of the specific gravity of the blood. 

11. Estimation of the number of blood plates. 

12. Estimation of the amount of fibrin. 

To describe these processes in detail is the purpose of the next 
chapters. 

I. Estimation of the Total Volume ok Mass of Blood. 

Until the present year the determination of the total mass of the 
blood has been practically beyond our reach, and our blood exami- 
nations have dealt wholly with small " samples " drawn from the 
^ See Chapter xiil. of Book II. 



6 



CLINICAL BLOOD EXAMINATION. 



peripliery and treated as typical of the rest without regard to any 
possible variations in the total amount of blood in the vessels. 

But recently Haldane and Smith, in three important and inter- 
esting papers, ' have suggested and applied a method which, if it 
stands the test of time and criticism, will add very materially to 
our knowledge of blood physiology and blood pathology. 

The essential features of their method are as follows : 

1. The patient inhales a measured volume of CO (a harmless 
and not unpleasant process). After two or three minutes a few 
drops of blood are taken for analysis and the percentage to which 
the haemoglobin has become saturated with carbonic oxide is esti- 
mated (by the carmine method, see reference at foot of page) . 

2. Knowing the amount of CO inhaled, and the degree in which 
the blood has become saturated by this known amount, the quantity 
of CO capable of being taken up by the whole of that patient's 
blood can be calculated. Thus, supposing that the volume of car- 
bonic oxide delivered was 150 c.c, and that the blood was twenty- 
five per cent saturated, it is obvious that the blood would have been 
one hundred per cent saturated by 600 c.c. Its total capacity 
for CO (or for oxygen) is 600 c.c. 

3. How then shall we connect this estimate of total oxygen 
capacity with the volmne of the blood ? In a previous research the 
writers showed that the oxygen capacity per 100 c.c. of any given 
sample of blood can be accurately estimated by comparing its color 
with the color of an equal sample of ox blood whose capacity for 
oxygen has been previously determined. For example, a patient 
having absorbed 100 c.c. of CO, it is found that his blood is one-fifth 
saturated by this gas. The total capacity for CO (and so for oxy- 
gen) is therefore 500 c.c. But further, the patient's blood is found 
to have the same color as an ox's blood every 100 c.c. of which 
has been previously determined to be capable of taking up 20 c.c. 
of oxygen. The patient's total oxygen capacity (500 c.c.) divided 
by the oxygen capacity of every 100 c.c. of his blood (20) gives us 
25. This figure is then the number of hundreds of cubic centi- 
metres of blood in his body — 2,500. 

Smith has now applied this method to over one hundred cases, 
and found it to produce no appreciable ill-effects on the patient. 
As the result of these studies, he estimates the average volume of 

^1. Journal of Physiology, xxii., p. 232. 2. Journal of Physiology, p. 
XXV., 331. 3. Transactions of the Pathological Society, 1900, vol. li. 



METHODS OF CLINICAL EXAMINATION. 



7 



blood in health as 3,240 c.c. or 3,420 gm. The latter figure is 
obtained by means of the average specific gravity of normal blood 
(taken as 1.055). In the fourteen normal cases studied the blood 
mass varied from 2,830 to 4,550 gm. or -g^ to yL- the body weight, 
but was never as large as had previously been estimated (yg-)- 

In chlorosis. Smith found that the apparent diminution in hae- 
moglobin was, in fact, due to the great increase in the plasma of 
the blood (serous plethora), the total oxygen capacity or hsemoglobin 
remaining normal. In pernicious anaemia, on the other hand, the 
amount of plasma is sometimes increased and sometimes dimin- 
ished, but the oxygen capacity or haemoglobin is always low. These 
observations will be referred to again later (see p. 131). 

II. Examination of the Fresh Blood. 

(a) Puncture. — In all the processes about to be described (ex- 
cept the bacteriological examination) the first step is as follows : 

Gently cleanse the lobe of the patient's ear with a damp cloth 
and then dry it. All vigorous rubbing or kneading is to be avoided. 
Attempts to sterilize the skin or to cleanse it with alcohol and ether 
are a waste of time. A small lancet or a bayonet-pointed surgical 
needle may be used ; a sewing needle gives more pain and draws less 
blood from a given depth of puncture. A steel pen, with one nib 
broken off, makes a good lancet. The needle need not be sterile. 
In several thousand blood counts made at the Massachusetts Gen- 
eral Hospital since 1893 the needles have never been sterilized and 
no signs of sejjsis have been seen in any case. 

Possibly this is due in part to the fact that the next step in the 
process after the puncture has been made is always to wipe away 
four or five successive drops as they emerge. This serves not only 
to get the blood flowing freely, but also to wash the ear in its own 
blood. 

The puncture is best made into the lower surface or edge of the 
lobe, which is steadied with the fingers of the left hand. A very 
quick stroke gives least pain, the hand rebounding like a piano 
hammer. If the skin of the lobe is stretched tight with the fingers 
of the left hand so that no " give " is possible, the quick puncture 
gives hardly any pain. I have repeatedly taken blood from a 
sleeping child without waking it. What hurts the patient is the 
mistaken tenderness that slowly ^wesses the needle through the skin. 



8 



CLINICAL BLOOD EXAMINATION. 



The puncture must be deep enough to make the blood flow freely 
and. without pressure, after it is once started by pressing out a few 
drops. Blood squeezed out with pressure should never be used for 
counting, as it may be considerably diluted with fluid pressed dut 
of the neighboring tissues. If the skin is moderately thin and the 
ear easily made hypersemic, a puncture one-eighth of an inch deep 
is suflicient. With thick, bloodless skin it may be necessary to go 
in one-quarter or one-third of an inch — never more. Beware of 
bleeders. I have seen bleeding from a puncture made for a blood 
count which could not be checked for three-quarters of an hour. It 
is always safer to ask after a history of haemophilia as a matter of 
routine before taking blood, just as one asks after false teeth before 
etherizing. If there is a history of haemophilia, a mere touch of 
the needle point will give us all the blood we need without embar- 
rassing us with a troublesome hemorrhage. 

There is no question as to the superiority of the ear over the 
finger for drawing the drop. The ear is less sensitive than the 
finger, and a slighter puncture gives us all the blood we need. 
Moreover, it is a distinct advantage, especially in children, that the 
patient cannot watch the puncture of the ear, or the preparations 
for making it, and cannot easily withdraw the part. A sleeping 
patient often needs to be roused to get at his finger, while his ear is 
usually easily accessible above the bed clothes. Again, the absence 
of any bony prominence against which to press makes us less likely 
to use too much pressure than if we puncture the finger. 

When one is makmg frequent examinations of the blood of a 
sensitive person, as in pneumonia, these details are of real impor- 
tance, and in cases of pernicious anaemia in which the previous 
attempts to get blood from the finger had been absolute failures, I 
have found no difficulty in getting it from the ear. In this disease 
the advantages of the ear over the finger are peculiarly great. 

P7'eparation of Temporary Specimens for Immediate Examination. 

(b) When, after wiping away the first four or five drops, a good- 
sized drop exudes spontaneously, touch the centre of a perfectly 
clean cover-glass against the summit of the drop without touching 
the skin itself at all, and drop the cover-glass face downward upon 
a slide so that the force of the impact will help to spread the drop of 
blood thinly and evenly between slide and cover. It is recom- 
mended by Ehrlich and others to hold the cover-glass with forceps. 



METHODS OF CLINICAL EXAMINATION. 



9 



but there is no harm in holding it with the fingers, provided we 
avoid touching either of its surfaces, i.e., hold it always as in 
Fig. 1.' 

Slide and cover must be perfectly clean, else the blood will not 
spread out in a layer thin enough to avoid the corpuscles overlying 
each other so that not one of them is 
clearly seen. Further, as dirt simulates 
fairly closely some of the pathological ap- 
pearances for which we are on the look- / / 

out, its presence on the slide leads to loss — -^..^^^^ ^ 

of time or to mistaken conclusions. Cover* 7^ 
glasses, as they come from the shops, may ) 
be coated with a substance not easily to 

be removed. To get them really clean fig. i.-Proper Method of how- 

° ^ ing a Cover-glass. 

nothing is so simple as or more effective 

than soap and water. After several years' use of the method 
of cleaning usually advised (viz., strong mineral acid, followed 
by alcohol and then by ether), I have become converted to the 
use of plain soap and water as the best and simplest way of 
cleaning slides or cover-glasses. E-ub soap over every part of the 
glass, wash it off with water, and polish it thoroughly with a clean 
handkerchief (most towels are apt to leave a scrap of lint on the 
glass). ^ If slide and cover are perfectly clean, are held as in Fig. 
1, and allowed to touch only the summit of the blood drop and not 
the skin, the blood will spread out properly between them, and no 
pressure on the cover-glass will be needed to make the layer of cor- 
puscles thin enough. Pressure is undesirable, as it often makes all 
sorts of artefacts in the preparation and hastens crenation of the 
red corpuscles. Better results are obtained if slide and cover are 
warmed just before using, and it is well to have an assistant rub the 
slide vigorously with a towel just before it is used. 

This method is, of course, applicable only to specimens to be 

' I am Dot unmindful of Ehrlicli's warning that the moisture of the lingers 
spoils the specimen; but in practice I do not find it to be true except as re- 
gards the margin of the film, the good preservation of which is not essential. 
Only the thinnest cover-glasses in the market should be used, | inch is the 
best size. 

■^Further experience has convinced me that water alone is generall}^ suffi- 
cient, provided the polishing, which is the chief factor of success, is thorough. 
Tissue paper is very useful for polishing cover-glasses. After polishing, it is 
well to pass them through a Bunsen or alcohol fiame once or twice. 



10 CLINICAL BLOOD EXAMINATION. 

immediately examined. Specimens whicli are to be transported or 
preserved should be prepared as directed on p. 43. 

Frevention of Cell-Death. 

Slides so prepared are usually best examined with a one-twelfth 
oil-immersion lens. As a rule they keep long enough for purposes 
of examination without any further precautions, but if we desire to 
keep the blood fresh and uncoagulated for a longer period, it is best 
to exclude air in this way: Paint upon the slide with vaseline, 
cedar oil, or any gummy substance a hollow square or ring of about 
the size of the cover-glass, so that when the latter with its drop of 
blood is put down upon the slide the drop will spread out inside the 
ring of oil, which seals the margins of the cover-glass to the slide. 
Specimens so prepared will keep for many hours unchanged, and 
without crenation or coagulation, if the weather is warm or if the 
slide be kept in a warm place. 

In examining blood suspected of containing malarial parasites it 
is sometimes useful to put the whole microscope into one of the 
warming apparatuses devised for the purpose. This is better than 
any of the various kinds of warm stage in use, but in clinical work 
there is rarely if ever any need for artificial heating apparatus of 
any kind, provided the room and the slide are warm. 

What Can be Learned from Fresh Blood. 

In the first place we note the readiness or sluggishness of its 
flow from a puncture of standard depth. The blood flows more 
readily than usual in the following conditions : 

1. Peripheral congestion or vaso-dilatation. 

2 Exaggerated fluidity of the blood (chlorosis, some types of 
anemia, and haemophilia). 

It flows sluggishly : 

1. After profuse hemorrhage or serous drain (cholera). 

2. In certain cases of extreme anaemia — e r/ , emaciated cancer 
cases. 

3. Vasomotor spasm (cold, hysteria, RajTiaud's disease, uraemia 
■ — certain cases). 

4. Exaggerated coagulability 

Examination of the fresh blood by the method described above 



METHODS OF CLINICAL EXAMINATION. 



11 



is also the best way known for ascertaining the presence or absence 
of— 

1. The Plasmodium malarise. 

2. The Spirochsete of relapsing fever. 

3. The Filaria sanguinis hominis. 

4. Kouleaux formation among the red cells. 

It is also a quick and convenient method of finding out with ap- 
proximate accuracy: 

(a) Whether the blood contains an increased amount of fibrin ; 

(b) Whether any considerable anaemia or leucocytosis' is present ; 

(c) Whether or not the amount of haemoglobin in the red cells 
is much decreased ; 

(d) Whether the red corpuscles are deformed ; 

(e) Whether the "blood plates " are increased or not. A prac- 
tised observer can also make a diagnosis of leukaemia by this method 
in most cases, but here mistakes may easily occur. 

So much can sometimes be learned from a specimen prepared in 
this very quick and easy way that it should be as much a matter of 
routine as a urine examination. But in order to get any information 
from such a preparation we must previously have familiarized our- 
selves with the appearance of normal blood under such conditions — 
with the size, shape, color, and refractions of the red cells, white 
cells, and blood plates and their ratio to one another, and with the 
great variety of curious phenomena to be seen as a drop of blood 
gradually dries up between slide and cover. No book can teach 
this ; it must be learned by actual experiment. 

Some of the commoner sources of error will be referred to later. 
Here I will mention only the Brownian movement in the protoplasm 
of the corpuscles, to be distinguished clearly both from the amoeboid 
movements of the leucocytes or of the malarial parasite and also 
from the irregular contractions of the dying protoplasm, which give 
rise to pseudo- amoeboid motions in the crenated points of normal 
red cells or in the irregular projections of corpuscles deformed by 
disease (vide infra). 

For a more detailed description of normal red corpuscles, white 
corpuscles, and blood plates the reader is referred to Part II. 

An account of the pathological changes to be observed in the 
fresh blood will be given in later chapters. 

^ More accurately it is only the ratio of red to white corpuscles that we 
can determine, and when the red are very much diminished in number we 
may be deceived into supposing that the white are increased. 



CHAPTER II. 



COUNTING THE CORPUSCLES. 



I. The Thoma-Zeiss counter. 

II. Dnrliam's moditied counter. 

I. Out of the many instruments devised for this purpose that of 
Thoma-Zeiss with Zappert's modified ruling of the counting 

chamber is the best, and much 
the most commonly used. In 
the use of this instrument there 
are five steps or stages : 

1. Puncturing the ear. 

2. Diluting and mixing the 
blood thus obtained. 

3. Adjusting a drop of di- 
luted blood in the counting 
chamber. 

4. Counting the corpuscles. 

5. Cleaning the pipette. 
"-^ To count the white corpus- 
cles, an instrument different 
from that employed for the red 
is often used. 

The technique is nearly the 
same for both instruments, but 
for clearness' sake I shall de- 
scribe them separately. To 
save time I shall call the small- 
bore pipette used for red cor- 
puscles (Fig. 2, .4) the "red 
counter," and the large -bore 



Fig. 3.— Thoma-Zeiss Pipettes. A. For red 
puscles ; B, for white corpuscles. 



pipette (Fig. 
counter." 



B) the "white 



COUNTING THE CORPUSCLES. 



13 



COUNTTXG THE ReD CoRPUSCLES 

(«) After puncturing the ear as above described, and as soon as 
the blood is flowing freely, put the point of the " red counter " into 
the drop as it emerges from the ear, and by sucking gently on the 
rubber tube attached to the other end, draw up blood to the mark 
0.5 on the pipette. It is convenient to rest 

the end of the pipette on the thumb as if;; 
shown in Fig. 3. It needs some practice J^li 
to stop exactly at the mark, but if we hap- 
pen to draw the blood up a little past the / ^.^4^ 




mark 0.5 no considerable error results, pro- 
vided we draw the column down again to 
the mark by tapping the point of the pipette 
on a towel, and provided also that the in- 
strument is perfectly clean and dry. The .^--^ /f7 
aim and intention, however, should always FiG.s.-Methodof Resting point 
be to stop exactly at the mark 0.5, and with ^^^^"^ ontheThumb while 

^ ' Sucking in Blood. 

a little practice we can do it, except with 

nervous or delirious patients, and those who carelessly move the 
head just at the critical moment. With such patients we usually 
have to content ourselves with drawing the blood a little beyond 
the mark 0.5 and then drawing it down again to the mark as above 
described. 

Diluting the Blood. 

(h) The bottle of solution to be used for diluting the blood 
should be ready uncorked at the bedside. Of the many solutions 
suggested by various authors none is better than Gotuev^s, the for- 
mula for which is as follows : 

Sodli snlpliat gr. 112 

Acid, acet 3 v. 

Aquce.. . § iv. 

Toisson's solution is also very useful and stains the white cor- 
puscles so that they can be easily distinguished from the red. Its 
composition is as follows : 

Methyl viokt, 5 B 0.025 gm. 

Sod. clilor 1.000 " . 

Sod. sulph 8.000 " 

Neutral glyceriu 30.000 cm. 

Aquse destill 160.000 " 



14 



CLINICAL BLOOD EXAMINATION. 



We must Tvait about ten minutes after mixing before the leucocytes 
are fully stained. Except for this delay, the only objection to this 
solution is that it is rather difficult to clean the pipette after using 
it. If the white cells are counted with another pipette the staining 
fluid can be as well dispensed with. 

Into a bottle of one of these solutions, ready at the bedside, the 
point of the pipette is to be plunged as soon as the blood has been 
drawn up to the point 0.5 and the outside of the pipette wiped clean 
of blood. Suction is then exerted through the rubber tube the in- 
stant the point of the pipette is below the surface of the diluting 
solution. This suction is continued until the diluted blood has 
filled the bulb of the pipette and gone past it up to the point 
marked 101. It is not difficult to stop at this point, provided the 
pipette is perfectly clean and dry inside. Otherwise it is impos- 
sible. Should any mishap occur at this point, the whole process 
must be begun over agai^i after carefully cleaning and drying the 
pipette. If no accident happens and the mixture is sucked up to 
and not past the mark 101, we have diluted the blood with two 
hundred times its bulk of neutral solution. If, instead of drawing 
the blood up to the mark 0.5, we draw it as far as the point marked 
1, and then dilute as above described, the mixture will be 1 to 100. 
Some observers habitually use this dilution. The objections to it 
are (1) That if the blood is accidentally drawn up too far {i.e., 
past the mark 1) we cannot draw it down again but must painfully 
clean and dry out the pipette (see below, p. 18) and repeat the proc- 
ess. (2) If the blood contain approximately the normal number 
of corpuscles, they will be so crowded when adjusted on the ruled 
surface of the disc A that it is more difficult to count them. If we 
use another pipette for the white corpuscles, the dilution of 1 : 100 
has no advantage to counterbalance these drawbacks. 

AVhile sucking in the diluting solution, it is well to roll the 
pipette on the long axis Avitli the fingers of tlie hand which holds it 
in the diluting fluid. This mixes the blood instantly and prevents 
any of it from floating on tlie top of the solution and thereby com- 
ing up undiluted into the narrow portion above the bulb of the 
pipette, where it might possibly escape thorough mixing.' 

, Next we thoroughly mix the blood and diluting fluid by shaking 
and rolling the pipette, its ends being closed by the fingers. Tlie 

^ Care must be taken that no saliva finds its way tlirougii the rubber tube 
and into the pipette. Xever bloAv throuu-h the rubber tube. 



COUNTING THE CORPUSCLES. 



15 



little glass ball within the bulb helps this process materially. A 
minute's brisk rolling and shaking is as good as five minutes', as I 
have convinced myself by many experiments, and the distribution 
of the corpuscles throughout the mixture is very even, provided 
there is no delay in proceeding to the next step,' viz. : 

(c) Adjusting a Drop of Diluted Blood in the Counting Chamher. 
— Remove the rubber tube from the pipette and blow out the por- 
tion of diluting solution which last entered the pipette, and which 
consequently has not been thoroughly mixed with the blood in the 
bulb. Five or six drops should be blown out before any is used for 
examination. Next put upon the surface of the counter (A, Fig. 
4) a drop of such size that when the cover-glass (B) is let down 



Fig. 4.— Thoma-Zeiss Counting Slide. A., Ruled disc ; B, cover-glass ; C, moat. 

over it, the whole of the disc A is covered with the drop without any 
being spilled into the "moat " (C) around it. Just how large such 
a drop should be, can be learned only by practice. It is not liter- 
ally necessary that exactly the whole disc A should be covered, 
provided nine-tenths of it is covered, but any spilling over into the 
"moat" (C) entails serious error. ^ 

After the cover-glass has been let down upon the drop, we 
should be able (provided the whole instrument is dean) to see con- 
centric rainbow rings between the cover-glass and the body of the 
instrument. These are known as Newton's rings, A little press- 
ure with a needle on the cover-glass will often bring them out if 
they do not at once appear, hut they must remain visible after the 
pressure is taken off. Otherwise we know that there must be some 
dirt or dust under the cover-glass preventing its settling exactly 

^ If we have to pause before going on to the next step, we must take care 
to roll and shake the pipette again when ready to proceed. 

2 In accordance with Meissen's suggestion Zeiss now supplies this apparatus 
with a groove in the glass disc outside the " moat, " whereby communication 
is established between the latter and the external air. Tluis the results of 
counting are made independent of differences in atmospheric pressure. 




'A 



c 



16 



CLINICAL BLOOD EXAMINATION. 



into position, and this will cause error in the count, though not a 
very considerable error in most cases. (To see Newton's rings we 
should get our eyes near to the level of the counting chamber so 
that the light from window or lamp is reflected from the surface of 
the cover-glass). 

If the above conditions are not all fulfilled, the instrument 
should be washed and another drop tried, after shaking the pipette 
and blowing out a few drops as before. 

The cover-glass must be let down as soon as possible after the 
drop has been put on the disc A, and before the corpuscles have 
time to settle. It is best to let it down with a needle as in mount- 
ing microscopic specimens. 

Counting. 

(d) After waiting two or three minutes so that the corpuscles 
may settle thoroughly upon the space ruled off on the disc A, the 

A 




Fig. 5.— Thoma-Zeiss Counting Slide. A, Ruled disc. 



counting is begun, using preferably an objective 5 of Leitz or D of 
Zeiss and a No. 1 or 2 eyepiece. 

The central part of the ruled space on the surface of Zappert's 
counting chamber (A, Fig. 5) is divided into four hundred squares, 
every group of sixteen squares being enclosed in double lines to 
make it easier to know how many squares we have counted (see 
rig. 6). Including the squares with double lines we have a group 
containing thirty-six small squares, a group convenient to count at 
one time as it just about fills the field of the objective Leitz No. 5, 
or Zeiss D with a No. 2 eyepiece. 

To avoid considerable error we should count the corpuscles in 
five fields of thirty-six squares each, such as is shown in Fig. 6, 



COUNTING THE CORPUSCLES. 



17 



taking the fields in various parts of the whole ruled space. Tiie 
instrument should then be washed ' and the whole process repeated 
with a second drop. If the count of the second drop differs widely 
from that of the first, a third drop should be counted, and the aver- 
age taken of those two which are most nearly alike. Thus at least 
three hundred and sixty small squares should be counted ; with such 
a number the error is not over three per cent for practised observers. 
In normal blood this means counting about 2,160 corpuscles, as six 
or seven to a small square ^ c 

is about the normal average 
when we are using a dilu- 
tion of 1 : 200 such as has 
been described (twelve to 
fourteen cells per square 
in a dilution of 1 : 100) . 

Among the difficulties 
encountered in counting is 
the presence of a few cor- 
puscles on or touching one 
or more of the lines hound- 
ing the space to be counted. 
Shall we count these out 
or in? 

In counting, for in- 
stance, a field like that in 
Fig. 6, what are we to do with the cells which sit astride the lines 
AA, BB, etc.? 

To get round this difficulty, it is best to make it a rule to count 
in all the corpuscles on or touching some two of the boundary lines 
{e.g., A A and BB) and to take no notice of any cell on or touching 
the lines CC and DD. In this way the exclusions just balance the 
inclusions. Of course all cells loithin these outer boundary lines 
are to be counted whatever their position. 

Beyond this the details must be settled by each man for himself. 
My own habit is to count through the squares in the order indicated 
by the track of the serpentine arrow in the accompanying Fig. 7, 
and to count by twos or threes. 

^ Use only water — alcohol dissolves the cement which holds the ruled disc 
in place. 

2 See Reinert's "Zahlung der Blutkorperchen, " Leipzig, 1891, p. 48 et seq. 

2 





0 


o 


o 


O 


o o 


o o 




o 




0 c 




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o 0 


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o 




o o o 
0 


> °o 


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o 


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o 




o 


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o — 


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o 


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° o° 

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°o° 


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o o 


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"5 o 


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) 00 O 


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o o ' 
oo n 


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A C 
Fjg. 6.— Field of Thirty-six Squares on Ruled Disc of 
Thoma-Zeiss Counter Covered with Normal Blood 
Diluted Two Hundred Times. 



18 



CLINICAL BLOOD EXAMINATION. 













































i 































































































J 










c 








— - 


















■^ 


















\ 















































A movable stage makes the counting easier, especially for be- 
ginners. Either natural or artificial light may be used, with a 
small aperture diaphragm, and if the instruments are clean and the 
diluting solution fresh and free from sediment,' there is no diffi- 
culty in deciding how many cells each square contains, and no ex- 
traneous fragments to be 
excluded. We must dis- 
tinguish the white corpus- 
cles from the red, not by 
their size but by their 
stain if Toisson's solu- 
tion is used, otherwise by 
their peculiar shining 
look when the lens is 
drawn up so as to put the 
red cells slightly out of 
focus. The blood plates 
are not noticeable and 
lead to no errors. 

When the number of 
corpuscles in 360 squares 
has been counted the 
number is divided by 360 and multiplied by 800,000 (i.e., by 200 
to make up for dilution and then by 4,000, because each square 
is equivalent to ^-qVo- ^ cubic millimetre), which gives us the 
number of corpuscles per cubic millimetre. 

These figures need not be committed to memory, for we have 
marked on the instruments used all the data necessary for the cal- 
culation, i.e., the dilution figures on the pipette and the area and 
depth of a single square on the counting slide, 

(e) The importance of cleaning the piioette as soon as the count- 
ing is done is so great that it should be reckoned as one of the 
regular steps on every count. First water, then alcohol, and lastly 
ether must be sucked into the pipette and brought into contact with 
every part of the bulb and tube. After this air must be sucked or 
pumped through the tube until it is perfectly dry and the glass ball 
will roll about freely in the bulb without sticking anywhere. 

These precautions take but two or three minutes, and if they are 

' Most diluting solutions precipitate or accumulate spores, and need to be 
frequently renewed or filtered. 



Fig. 7.— The Arrow Indicates the Order in which the 
Squares are Counted. 



COUNTING THE CORPUSCLES. 



19 



omitted and the blood dries in the pipette, it may take several 
honrs' work to get it clean. Further, if it is not thoroughly dried 
after cleaning, the mixing of the blood when it is used next cannot 
be done accurately. 

The first three steps of the above process {i.e., the obtaining, 
diluting, and mixing of the blood) must be done as swiftly as is 
compatible with accuracy, but when once the blood is mixed in the 
pipette it can be kept there indefinitely and counted at leisure. 
Xone of the corpuscles are destroyed or lost, and if the bulb is 
thoroughly rolled and shaken up whenever we are ready to count 
the blood, no error results from keeping it twenty-four hours or 
more in the pipette. 

It is not necessary, therefore, to carry a microscope to the pa- 
tient's house or bedside; the pipette and the diluting solution are 
all that we need to take with us, and when the blood is mixed in 
the pipette, the latter' s ends can be closed with a rubber band, and 
the blood carried home and counted at leisure. The pipette should 
be kept approximately horizontal during the transit. 

COUXTIXG THE WhITE CoRPUSCLES. 

To make a reasonably accurate count of white corpuscles, using 
the " red counter " and the dilution of 1 ; 100 or 1 : 200, we need to 
count an immense number of squares, far more than was necessary 
m estimatmg the red cells — in fact, at least ten times the whole 
ruled space. It is therefore far quicker and more accurate to use 
the "white counter" or large-bore pipette with a diluting solution 
which renders the red cells invisible and leaves onl}' the white to be 
counted. Such a solution is the one-half of one-per-cent solution 
of glacial acetic acid in water. With this the white corpuscles 
stand out very clearly and the red can barely be seen at all. The 
technique is the same as that already described, with the following 
exceptions : 

1. The drop of blood needed is nearly three times as large as 
that used in the " red counter " ; it is about as big as can be made to 
stay on the ear without rolling off, even if we draw blood only to 
the mark 0. 5. If we draw blood to the mark 1, as ad^T.sed by Tlirck-, 
we must make a deeper puncture and suck in the blood as it flows 
without waiting for the formation of drops . 

2. The bore of the tube being large, it fills and empties more 



20 



CLINICAL BLOOD EXAMINATION. 



readily. Hence our suction must be gentler, and. it is rather harder 
to stop exactly at the mark 11. For the same reason the diluted 
blood will run out of the pipette if the latter is not kept nearly 
horizontal, and the bottle of diluting solution should accordingly be 
tipped up as we plunge in the point of the pipette, so that the latter 
is depressed as little and for as short a time as possible before suc- 
tion begins. 

3. Zappert's modification of the Thoma-Zeiss counting chamber 
should be used. Zappert's counting chamber (now supplied by 
Zeiss at the same price as the ordinary one, i.e., 15 marks) differs 
from that ordinarily used in that the central square millimetre is 
surrounded by eight undivided squares of the same size (see Fig. 
10). With this ruling one counts first the number of leucocytes in 
the central square (about 35 in normal blood) and then in each of 
the surrounding undivided squares. This gives us a total of about 
300 leucocytes (in normal blood) as a basis for our calculations. 
The total so obtained is divided by 9, and then multiplied by 200 
(provided we have diluted 1 : 20). 

The advantages of the large-bore pipette are obvious. The only 
drawback is its expanse. The technique is not at all difficult. 

Counting Both Red and White Cells with the Same Fipette. 

We may avoid buying both large-bore and small-bore pipettes in 
one of the following ways : 

1. We can count both red and white corpuscles with the " red 
counter. " 

2. We can count both red and white corpuscles with the " white 
counter." 

The reason why we cannot use the " red counter " for counting 
white cells, unless modified in some way, is that in the whole ruled 
surface of the counting chamber not more than three or four white 
corpuscles are to be found in normal blood when diluted two hun- 
dred times. If we dilute less, we cannot see the cells distinctly, 
because they^are so crowded. If we find, say, three white corpus- 
cles as the number to be used as a basis in calculating the number 
of white cells in a cubic millimetre, the chance of error is very 
great, the multiplier being so large (2,000) and the multiplicand so 
small (3). 

To get over this difficulty we may utilize the cells spread over 



COUXTIXG THE CORPUSCLES. 



21 



the disc of the counting chcunber outside the ruled sjxtce in one of 
the following ways : 

(a) By Pleasuring the JreJd of the ohjertlee used. The writer's 
objective, No. 5 of Leitz, has a lield of very nearly one-quarter of 
a square millimetre or one-quarter of the whole ruled space. Four 
fields of this lens, taken anywhere outside the ruled space, there- 
fore, contain the same number of cells as will cover the whole four 
hundred small ruled squares, and ^vhen we have counted the Avhite 
cells in a series of four fields of this lens, we have accomplished as 
much as if we have put a fresh drop upon the counting chamber and 
counted all the ruled squares over again ; the latter process is 
tedious, the former 
very quick. Thus it 
is my practice in some 
cases to proceed as 
follows (see Fig. 8) : 
Supposing the large 
circle CCCC to rep- 
resent the surface of 
the small disc (A, 
Fig. 4) in the centre 
of the counting cham- 
ber, and AAAA the 
ruled squares in the 
middle of this disc, 
four microscopic 
fields are taken in the 
direction away from 
the centre indicated 
by circles and arrows in the figure. Starting, say, to the right of 
the ruled squares with the left edge of the microscopic field just 
touching the outer boundary line of the squares, count all the white 
cells to be seen in the field. Then move along to the right till the 
corpuscles which were on the extreme right of the first field have 
gone out of sight to the left. Your field is then in the position 
of the circle marked 2 (Fig. 8). Coimt all the white cells in this 
field and so on for four fields. With my objective, four such 
fields are almost exactly equal to the whole ruled space AAAA. 
With other objectives of course the number of fields is different. 

A\Tien we have counted four fiehls in each of the four directions 




* 



22 



CLINICAL BLOOD EXAMINATION. 



iiidica.tecl by the arrows ^ve liave covered as iiiueli ground as if we 
have put four successive drops on the slide after the first one and 

counted all the ruled squares in each, and 
we have saved much time and labor. 

(I)) Another and better method of at- 
taining this same end is as follows : Cut 
out of black cardboard a piece of the 
shape shown in Fig. 9 and of such a size 
that it will fit into the tube of the eye- 
piece — the sqnare aperture allowing a 
space of just one -quarter of a millimetre 
(one hundred of the ruled squares) to be 
seen through it with a given objective (say 
Leitz Xo. 5) . Four fields as seen through such an aperture can 
then be connted in various parts of the slide outside the ruled space 
as explained above. 

(c) For any one livmg where microscopic ruling on glass can be 
done at a moderate cost, by far the best way is to have the rest 



a 




Fig. 10.— Zappert's Countingr-cliamber. 



of the disc A (Fig. 5) ruled off as shown in Fig. 10. Leitz and 
Zeiss now supply instruments so ruled. I have not been able to 
hear of any one in America who could do such work at a moderate 
expense. 




• 



COUNTING THE CORPUSCLES. 



23 



(d) We may work out matliematically what number of squares 
would be contained on the whole disc were it all ruled like the cen- 
tral portion. This can be done with the aid of a micrometre eye- 
piece and a mechanical stage. There is some variation in individ- 
ual instruments, but as a rule the disc outside the central ruled 
space has an area of about two thousand of the small squares. 

2. We may use the " white counter " for red corpuscles in the 
following way : Suck up blood only to the first mark up from the 
point (i.e., one-fifth of the usual distance) and then Gowers' orTois- 
son's solution up to the mark 11. This gives a dilution of 1: 100, 
and in anaemic cases, in which the cells are not very numerous, 
answers well. The same pipette can then be carefully cleansed and 
used for counting white cells with the acetic acid one-third per cent, 
and a dilution of 1 : 10 or 1 : 20. 

Whatever method of counting white corpuscles is adopted, we 
ought to have at least one hundred corpuscles actually counted to 
use as the multiplicand of our computation. A single drop from 
the white counter with a dilution of 1 : 10 gives us normally about 
seventy white corpuscles in the four hundred ruled spaces, and by 
repeating the process with a second drop the result may be made 
reasonably accurate. This was the method adopted by Eieder' in 
the immense number of counts made by him. 

II. Durliam^s Modified Hcvmocytometer. 

In the Edinburgh Medical Journal for October, 1897, Herbert E. 
Durham, of Cambridge, England, describes a self-filling capillary 
pipette which has considerable advantages over the ordinary Thoma- 
Zeiss instrument. The account of the device is here given in his 
own words. 

" The apparatus entails no new principle ; it is rather to be con- 
sidered as an adaptation of a number of details, which together seem 
to present some advantages. As in the Gowers' instrument, there 
is a separate capillary pipette for measuring the blood, one for 
measuring the diluting fluid, a mixing vessel, and the counting 
chamber. A few words may be said about each of these. 

" Capillar u Pipette. — There is an obvious advantage in the use 
of a self -measuring pipette. It cannot go wrong by accident. 
Durham has availed himself of the pipettes introduced by Dr. 
Oliver, namely, small pieces of thick-walled capillary tube — 5 and 
' "Beitrage zur Kenntniss der Leucocytosis," Leipzig, 1892 (Vogel). 



24 



CLINICAL BLOOD EXAMINATION. 



10 c.mm. Ill capacity. Tliese are carefully recalibrated by the 
makers of Dr. Oliver's instrument —T lie Tintometer Compan}^ 

There is, moreover, another important advantage attaching to 
Dr. Oliver's pipette; this consists in the readiness ■\vith which it 
may be cleansed. As he has described, all that is necessary is to 
pass a piece of darning cotton by means of a needle through the 
^ bore of the pipette. All the adherent serum, etc., is completely 
removed thereby. Durham generally ^vets the end of the cotton 
T^'ith ether, but this is not absolutely necessary. In passing the 
needle, it is better to pass it into the pointed end, in case it is not 
withdrawn perfectly axially, when there is a liability to chip the 
thinner unsupported glass. 

"Any one who has worked much with the Thoma-Zeiss pipette 
will know how troublesome it is to clean, especially when a number 



Fig. 11. — Cross- section of Durham's Automatic Blood- Pipette. T. Glass tube (like that of 
medicine-dropper) ; JV, rubher nipple (like that of medicine-dropper) : perforation in the 
nipple ; c, cork holder, perforated hy capillary pipette. 

of observations have to be made in a limited time. Unless it is 
frequently cleaned out with strong acid, there is a tendency for the 
deposition of sticky serum remains which interfere with true read- 
ings. 

'"For use. Dr. Oliver's pipettes are mounted by means of a small 
cork {c) ill a large glass tube (T), which is provided with a rubber 
nipple (A") J having a lateral perforation (j^) C^^S- H)- 

"•'The mixing vessel consists of a small test tube (2|- x yV 
1 c.c, or 2|- X f in. for i c.c). Several such tubes may be kept, 
so that a number of observations can be made if necessary. For 
thoroughly mixing the blood and diluting fluid, one or more small 
glass globules are placed in the tube. B}- using different colored 
glass globules, different specimens can be readily differentiated. 

"For measuring the diluting ^ui^, pijoettes containing 1 and -|- 
c.c. are used; these are remarked at 995 and 990 c.mm. and 495 
and 490 c.mm. respectively. With these graduations the following 
dilutions may be obtained : 1 : 200, 1 : 100, and 1 : 50, with the a^D- 
propriate capillary pipette. 




T. 




COUNTING THE CORPUSCLES. 



25 



" Having measured the diluting fluid, according to the eventual 
dilution desired, the blood capillary is filled by touching the ex- 
uding dro23 of blood and allowing it to completely till itself. The 
blood may be obtained in the usual manner from the lobule of the 
ear, the first drops being wiped away. 

" The hole in the nipple allows free air-way so that there is no 
hindrance to the action of capillarity. When filled, any blood on 
the outside of the pipette is rapidly wiped off, and the tube is in- 
serted into the mixer until the point is one-half to three-fourths of 
an inch above the level of the contained liquid. 

" The nipple is then held in such a way that the hole lies under 
the thumb of the operator. When this is the case it is slightly 
squeezed, and then, while the pressure is continued, the bulb is 
rotated so that the hole is free again. In this way the blood is 
sqnirted out, but not sucked back again. The procedure is ex- 
tremely simple and really requires no practice, given an operator 
who is not possessed of ' five thumbs.' In order to wash out the 
remains of the blood the point of the capillary is dropped into 
the diluting fluid ; the bore instantly fills itself. It is then with- 
drawn and 'the pressure and rotation of the nipple are repeated. 
This has to be repeated several times, and occupies a few seconds 
of time. It has been suggested that a certain amount of error is 
introduced by measuring the diluting fluid in a pipette, the inner 
surface of which retains some moisture ; this is extremely small in 
amount if the pipette is emptied slowly, and comparative readings 
with the Thoma-Zeiss apparatus show that the error is negligible. 

" To mix the blood and diluting fluid thoroughly, the mixer is 
placed between the opposed hands, which are rubbed backward and 
forward ; the mixer is rotated thereby, and the glass globules cause 
a thorough dispersion of the corpuscles in the fluid. 

"A drop of sufficient size is then placed upon the counting 
chamber, and the cover-slip is slipped on sideways in the usual 
way. I prefer the Thoma-Zeiss counting chamber. 

" The advantages of this method are : 

" 1. The ease and thoroughness with which the pipette can be 
cleaned. 

"2. The manifest advantage of the self -measurement of the 
blood. 

" 3. The avoidance of the objectionable necessity of nsing the 
mouth to suck fluids into the pipette. 



26 



CLINICAL BLOOD EXAMINATION. 



" 4. The measurement of the dikient can be done carefully and 
calmly beforehand, and any error corrected without taking any more 
blood. 

o. The greatly smaller cost of the pipette. 
" 6. The same pipette is useful for making various dilutions in 
serum diagnosis, by using several mixing vessels filled beforehand 
with dilute fluid," 



CHAPTER III. 



OLIVER'S H^MOCYTOMETER— CENTEIFUGALIZING THE BLOOD 
— H^3I0GL0BIN ESTIMATION— SPECIFIC GRAVITY— 
STAINED SPECIMENS— BACTERIOLOGICAL 
EXAMINATION. 



Recextly a inetliocl of estimating corpuscles by means of tlieir 
optical effect, and without directly counting them, has been intro- 
duced by Dr. Oliver. For practical purposes an actual counting of 
the corpuscles must be considered a necessity; not only since the 
number of leucocytes is not without importance (e.^., in the diag- 
nosis of enteric fever) , but also since these cells may be so abundant 
that they may interfere with the use of optical methods, as in the 
case of leukaemia. Nevertheless the instrument is very accurate 
and useful in many cases. Its principle is based on the fact that 
if a small quantity of blood is gradually diluted Avith Hayem's solu- 
tion' in a test tube whose sides are flattened so that its mouth forms 
a rectangle about 15 mm. by 5 mm., and a candle flame is looked 
at through the mixture, there is to be seen, when a certain degree of 
dilution is reached, a bright horizontal line on the glass. This line 
is made up of a large number of minute images of the flame, pro- 
duced by the longitudinal striation of the glass. If the quantity 
and quality of blood used are in every instance the same, the degree 
of opacity depends wholly on the amount of Hayem's solution added. 
It is found that with normal blood the amount of diluting solution 
necessary to allow the image of the candle flame to be seen through 
the mixture is always the same, and can be very accurately fixed, so 
that a variation of one per cent in the number of corpuscles can be 
distinguished by noting the amount of diluting solution which must 

' H^Tlrargyri perchloridi 0.5 gm. 

Sodii chloridi 1-0 " 



Oliver's H.^:mocytometer. 



" sulphatis . 
Aqufe destiflatse 



50 " 
200.0 c.c. 



28 



CLINICAL BLOOD EXAMINATION. 



be added before the image of the flame appears. To collect the 
blood. Oliver uses a capillary pipette containing about 10 c.mm. (one 
large drop\ and used exactly in the same way as the v. Fleischl 
capillary pipette (see Fig. 12). 

One pipette full of normal blood is gradually diluted in the flat- 
tened tube with Hayem's solution until a bright horizontal line 




Fig. 12.— Oliver's Hteraocytometer. A, Graduated mixing txibe; P. capillary pipette: J/, 
dropper, with rubber nozzle fitting tbe capillary pipette. 

caused by the image of candle flame becomes visible through the 
mixture. The point to which the column of the mixture then 
reaches is marked 100, and the space between that point and the 
bottom of the tube is divided into 100 equal parts. The point 
marked 100 is then equivalent to 5,000,000 red corpuscles; 90 = 
4,500,000, 80 = 4,000,000, and so on, each degree on the scale ' 
corresponding to a difference of 50,000 corpuscles (Fig. 12). 

Use of Oliver's Hcemocijtometer. 

The capillary pipette is first thoroughly cleaned and dried by 
passing through it a needle and thread saturated with water and 
then with alcohol and ether. It is then filled in the usual way, 



Oliver's h.^:mocytometer. 



29 



and the outside carefully and quickly wiped if necessary. The 
medicine dropper (previously filled with Hay em solution) is then 
connected with the polished blunt end of the pipette by means of 
the rubber tube (Fig. 12)^ and blood washed into the test tube. 
Speed is essential, else coagulation occurs. If the previous hasnio- 
globin estimation, has shown ninety to one hundred per cent of color- 
ing matter, we can safely add the diluting solution rapidly until the 
point marked 80 is reached. 
If the colormg matter is 
lower we must cease our 
rapid dilution correspond- 
ingly sooner. AVhen we get 
near the point at which the 
flame image is likely to 
appear, the diluting fluid 
must be added a few drops 
at a time. After each addi- 
tion put the thumb over the 
mouth of the tube and 
turn it upside down once 
or twice to mix the blood 
thoroughly, w i p i n g the 
thumb each time on the 
edge of the tube so as to 
put back what fluid has ad- 
hered to it. At a eertani 
point the image will sud- 
denly become visible. It 
is seen soonest if we rotate 

the tube on its lono' axis the Method of Holding Oliver's 

. ' . ' Haemocytometer. 

as the image becomes visible 

earliest at the sides of the tube, but dilution should be continued 
drop by drop until the horizontal line of light is just visible across 
the short diameter of the tube. The appearance of the incom^olete 
line at the sides is a constant forerunner of the complete transverse 
Ime, and should put one on one's guard as very close watching is 
needed to recognize it without overstepping the necessary dilution. 
The opacity remains uniform for many minutes. The whole process 
should be carried on in a perfectly dark room, and the diffused light 
of the candle must be shut off from the eye. This is best done by 




30 



CLINICAL BLOOD EXAMINATION. 



fitting tlie tube into the hand as shown in Fig. 13 with the long axis 
in line with candle, holding the tube close to the eye^ and standing 
about ten feet from the candle. In the use of both of his instruments 
Oliver employs only the small wax candle known as Christmas can- 
dles, whose flame is of the most convenient size. 

After some experience with this instrument I find it simple, 
accurate, eye-saving, and rapid. The whole test can be made in 
five minutes. Its only drawback is the impossibility of making any 
estimate of the white corpuscles with it. Dr. David D. Scannell 
made in 1899 ' a series of observation on patients in my clinic, to 
test the accuracy of the instrument when compared with actual counts 
made with the Thoma-Zeiss apparatus. As will be seen by the 
accompanying table, his results showed that, exclusive of leukgemic 
casesj the difference in the readings of the two instruments was 
from 4,000 to 74,000 red cells, an average of 35,000. This implies 
an error of less than one per cent, granting that the Thoma-Zeiss 



No. 


Diagnosis. 


Thoma-Zeiss 
red count. 


Oliver's hgemocj'tometer 
reading = red corpuscles. 


Remarks. 


1 


Pernicious anaemia. . 


1.704.000 


32 per cent. 


1,700.000 




2 


Debihty (?) 


4,368,000 


87 " 


4.350.000 




3 




4,626,000 


92 




4,600,000 




4 




2,492,000 


52 




2,600,000 


Whites, 480.000 


5 




4,734,000 


95 




4,750,000 


6 




2,579,000 


51 




2,550.000 




7 


SvplnUs 


4,428.000 


90 




4500,000 




8 


Secondary anaemia. . 


2,632.000 


52 




2,600,000 




9 


Pernicious anaemia. . 


1,178.000 


24 




1,200,000 




10 


Lympha?mia 


3.726.000 


73 




3,650,000 


Whites, 102,400 


11 




5.024.000 


99 




4,950.000 




12 


Pernicious anaemia. . 


2.907.000 


59 




2.950.000 




13 


Normal 


5,136.000 


102 




5.100,000 




14 


Pernicious anaemia. . 


2.934,000 


59 




2,950.000 




15 


Debihty (?) 


4,784 000 


96 




4,800,000 




16 




5.000,000 


99 




4950,000 




17 


Pernicious anaemia. . 


1.596.000 


32 




1,600.000 




18 


Debility (?) 


4.584000 


92 




4,600,000 




19 


Chlorosis 


3.583.000 


71 




3,550,000 




20 


Gastric cancer 


4080.000 


81 




4,050.000 




21 


Secondary anaemia. . 


4.120.000 


82 




4100.000 




22 






109 
82 




5.450.000 




23 


Gastric cancer 


4120.000 




4100,000 




24 


Debihtv (?) 


4.824000 


96 




4800.000 




25 


Pernicious aDa?mia. . 


1.976.000 


40 




2.000.000 




26 


Raynaud's disease. . 


3.486.000 


70 




3,500.000 




27 




4268,000 


85 




4,250.000 





^ Boston Med. and Surg. Jour., February 15th, 1900. 



CENTRIFUGALIZING THE BLOOD. 



31 



instrument was exactly correct, in each case. In many of these 
cases I verified Dr. Scannell's readings and counts. 

Dr. G. W. Fitz finds that the degree of dilution necessary to make 
the bright horizontal line appear corresponds with fifty-two corpus- 
cles to every thirty-six squares of the Thoma-Zeiss counter. This 
means that if a drop of the mixture be placed on the Thoma-Zeiss 
counting chamber^ just after the bright line appears, fifty-two cor- 
puscles are to be found in thirty-six squares. If more or less are 
found the dilution has been proportionally incorrect. 

The H.^:matocrit. 

The hsematocrit of Hedm has undergone considerable modifica- 
tion and improvement and as remodelled and improved by Judson 
Daland has been used to some extent in this country. Its direct 
and obvious object is simply to ascertain the relative volume or 
mass of the corpuscles and of the plasma in a drop of blood ; but 
the hope of its advocates has usually been that it would supplant 
entirely or mostly the long, tedious, and eye-destroying process of 
counting with the Thoma-Zeiss instrument. 

To use the Daland heematocrit we prick the ear as usual and 
with the help of a bit of rubber tube attached to one end of the 
capillary tube (Fig. 14) suck in enough blood to fill it entirely. 

As soon as it is full, put the finger (greased with vaseline) 
tightly over the free end of the glass tube and then, but not till tlien, 
draw off the rubber tube and adjust the glass as quickly as possible 
in the place prepared for it on one of the horizontal arms of the 
whirling machine (Fig. 14). A similar tube (empty) should be put 
on the other arm of the crosspiece to make the balance true. The 
handle of the instrument is then revolved at least seventy times a 
minute for two minutes, at the end of which time (sometimes less) 
the column of blood cells is packed so tight that no further whirling 
has any effect on its length. 

To estimate the number of red corpuscles from the length of the 
column, we call each degree of the scale on the tube 100,000 cells, 
or a little more. Thus if the blood column in the tube ends at 
about the mark 50, we consider that the blood has rather more than 
5,000,000 red corpuscles per cubic millimetre. So far all observers- 
agree on the figures, but as to just how much more or less than 
100,000 each degree on the scale is worth there is some variation 



32 



CLINICAL BLOOD EXAMINATION. 



between different observers. Daland ^ finds that the degree of the 
scale on the capillary tube corresponds to 99,390 corpuscles. 

So far as I can learn, the use of this instrument in Europe has 
been chiefly fo]' the direct information it affords as to the ajlume of 

the red cells and the amount of re- 
spiratory surface in the blood, rather 
than for the indirect information it 
may give ns as to the numher of the 
red cells. It does not seem as yet to 
be supplanting the Thoma-Zeiss coun- 
ter. 

Its bulk and the noise it makes 
must for the present, I think, prevent 
its extensive use outside of hospitals. 
The noise it makes is a very loud and 
disagreeable one, and will deter many 
from using it in private practice. 

H.t:moglobix Estimatiox. 

1. Tallqvist's Heemoglobinometer. 

2. Dare's 

3. Oliver's 

4. V. Fleischl's 

Until recently the instrument most 
used both here and in Europe was that 
of V. Eleischl. In France Hayem rules 
supreme in the matter of instruments, 
as in everything else concerning the 
blood, and in England Oliver's apparatus is used to a certain ex- 
tent. \Yithin a year, however, a contrivance originated by Tall- 
qvist - has come into use and deserves, in my judgment, to sup- 
plant all others in clinical work. I shall therefore describe it first. 

I. Tallqvisfs Hcemoglohinometer. 

A drop of undiluted blood is soaked into a bit of filter paper of 
standard quality and compared (by ordinary reflected daylight) 
with a paper color-scale of ten tints, ranging from ten per cent to 

'University Med. 3Iag.. Xovember, 1891. 
2Tallqvist,'St. Paul Med. Jour., May, 1900. 




Fig. 14.— Dalancl"s Hgematocrit. Two 
capillary tubes in place on the hori- 
zontal whirling beam. The instru- 
ment is to be fastened to the edge 
of some soUd and bulky piece of 
fm'niture by means of the thumb- 
screw seen at the bottom of the cut. 
If not very tightly secured, it will 
work loose when the handle is re- 
volved rapidly. 



HAEMOGLOBIN ESTIMATION. 



33 



one hundred per cent. The scale was prepared by imitating in 
water color the tint of the blood of anaemic patients (using the v. 
Fleischl instrument) when soaked into the standard filter paper. 
The water-color standard colors were then reproduced in lithograph, 
and the lithographed scale bound up with fifty sheets of the stand- 
ard filter paper makes an apparatus which can be easily slipped into 
the pocket and carried to the bedside. 

In making the comparison the blood stain is put against a back- 
ground of white filter paper beside the color scale, and moved along 
until a match is found. The comparison should be made as soon as 
the stain has lost its humid gloss, and before it is thoroughly dry. 
Artificial light cannot be used. Errors of ten per cent are possible, 
but it is my belief that far greater errors than this are frequently 
made with v. Fleischl's or Oliver's instrument in the hands of the 
great, majority of physicians. Tallqvist's scale costs but $1.25, 
and can be used by any one with sufficient accuracy for practical 
purposes, and with a celerity that makes haemoglobin estimation no 
more of an undertaking than feeling the pulse. I have used the 
instrument in several hundred cases, and have never yet been mis- 
led by it, nor found a greater error than ten per cent in comparison 
with Oliver's instrument. 

//. Dare'' 8 ^ Hcemoglohinometer. 

This excellent instrument is undoubtedly more accurate than 
Tallqvist's, and would be preferable to all others but for its cost 
($20), its bulk, and the time necessary to make an observation and 
to clean the parts. 

As in Tallqvist's method, undiluted blood is used, and this con- 
stitutes an advantage over both v. Fleischl's and Oliver's instru. 
ments. The blood is drawn by capillary attraction into the slit 
between two slabs of glass, one transparent, the other translucent 
and white, so as to diffuse the light used for illumination. 

The color of the blood is then compared with different portions 
of a circular disc of colored glass revolved by means of a thumb 
screw so that different tints are successively brought side by side 
with the blood tint. Transmitted light from a candle is used for 
illumination, and the observation is made through a telescoping 
camera tube excuding all extraneous light. As we turn the screw 
and bring different tints of the glass standard into comparison with 
'Phila. Med. Jour., October, 1900. 

3 



34 



CLINICAL BLOOD EXAMINATION. 



the layer of undiluted blood, the percentage of haemoglobin can be 
read off from the etched scale which appears at a point opposite the 
color apperture. The sharply bevelled edge of the opening rests 
directly over the reading indicated. A pivoted black screen pro- 
tects the observer's eyes from the direct light of the candle, and may 
occasionally be brought over the color apertures so as to rest the eye. 

The instrument is so made that blood film and standard color 
disc are viewed side by side in a horizontal plane through two cir- 
cular holes 5 mm. in diameter which are considerably magnified by 
a lens in the telescoping camera tube. 

In. using the instrument we need no dark room — a great advan- 
tage. The instrument is simply pointed at some dark surface — a 
dark coat or corner. In order that the blood and the color disc 
should be equally lighted, it is essential to see that any curve that 
exists in the candle wick should point straight toward or away 
from the centre of the instrument in line with the juncture of the 
springs which support the candle. 

The reading should be completed before the blood film begins to 
shrink in from the edges, i.e., within ten minutes. 

The advantages of Dare's instrument are: 

1. Its accuracy ; using undiluted blood and making allowance as 
it does for the color curve, it is, I believe, more accurate than any 
other clinically available instrument. 

2. Leucocytosis does not disturb the reading (as it does in v. 
Fleischl's instrument). 

3. The errors and waste of time incident upon dilution are 
avoided since the instrument uses undiluted blood. 

4. No dark room is needed. 

5. It can be used and cleansed much more quickly than any 
other instrument except Tallqvist's. 

My reason for preferring Tallqvist's mstrument despite these 
merits of Dare's are: 

1. Because accuracy greater than that obtainable with Tallqvist's 
instrument, is seldom practically important. 

2. Because an observation can be made with Tallqvist's hsemo- 
globinometer in about one one-tenth of the time needed for using 
any other instrument, i.e., in about twenty-five seconds. 

3. Because the Tallqvist instrument takes so little room and 
needs no cleaning or preparing for use. 

4. Because it is so cheap. 



HEMOGLOBIN ESTIMATION. 



35 



III. Oliver^ s Hcemoglobinometer. 

Oliver's instrument corrects two errors which are inherent in v. 
Fleischl's. 

1. It has no sliding scale of color, but compares the blood tint 
successively with definite tints of glass, each of which is even. 
The tints are worked out to correspond to the specific dilution 
curve of blood, for : 

2. Since every colored liquid changes color at a different rate 
when diluted, the dilution curve of blood does not correspond to 
that of glass (which behaves in this respect like a liquid). The 
glass wedge of v. Fleischl's Instrument represents a single color 
regularly diluted and does not correspond in its degrees to the 
colors of blood diluted at a similar rate. The scale of Dr. Oliver's 
instrument is measured to correspond to the actual colors of the 
blood's dilution curve, by means of the tintometer. 

In other respects the principle of the instrument is like v. 
Fleischl's, and the method of using the two is practically the same 
except that in Oliver's reflected light is used instead of transmitted 
light. Oliver's instrument consists of a series of twelve tinted glass 
discs corresponding to the haemoglobin percentages from 10 to 120 
and arranged in two rows (see Fig. 15, a). The intermediate degrees 
are measured by means of " riders " of colored glass, which can be 
laid on top of the primary color discs so as to deepen the tint 
seen. 

The capillary pipette (Fig. 15, h) is somewhat stouter than v. 
Fleischl's, but is used in the same way to collect the blood, which is 
then forced out of it with water from a medicine dropper (which is 
fitted with a rubber tube to slip over the blunt end of the pipette) 
(Fig. 15, c) and washed into a mixing cell (Fig. 15, d) similar to v. 
Fleischl's, except for the absence of a central partition. Here the 
blood is mixed in the usual way with water and the cell filled to 
the brim and covered with a small glass plate ; a bubble always 
forms, but by turning the cell or moving the cover-glass we can 
usually get the troublesome shadow thrown by the bubble out 
of the color field. The blood thus prepared is brought close 
to the scale and there compared with the tint of the different 
standard color discs. If it matches one of them the observation 
is complete ; if not we use one of the glass riders which enables 
us to read within two and a half degrees. A fuller set of riders 



36 



CLINICAL BLOOD EXAMINATION. 



can be obtained so as to make it possible to read down to one per 
cent. 

The standard is usually arranged for candle-light, but another 
set of discs can be obtained adjusted to daylight readings. The 
latter are less accurate. The same precautions as to the exclusion of 
outer light by means of a " hydroscope " tube, resting the eye fre- 
quently, etc., must be observed with this instrument as with v. 
Fleischl's. [It can be obtamed of J. H. Smith & Cie., Zurich 



c 




Fig. 15.— Oliver's Hgemoglobinometer. a. Standard cclor discs ; b, capillary pipette ; c, washing 

tube ; f7, mixing cell. 

(Wollishoften), for 115 francs plus duties and expressage, or of the 
Tintometer Company, 6 Farriugdon Avenue, London, E. Co] The 
candle should be placed three or four inches from the instrument 
and arranged to light both the blood and the color discs alike. 

A word as to the use of the riders. The instrument as used for 
clinical work usually has two riders : the one having the deeper tmt 
is used on the upper half of the scale, the other on the lower. 
Suppose we have decided that the blood color is between 60 and 
70. Put the rider on the 60 disc and compare again. If the blood 
is darker than the 60 disc plus the rider, the percentage is approxi- 
mately 671 (since it is higher than 60 -f- 5 [the rider] and lower 



HAEMOGLOBIN ESTIMATION. 



37 



than 70). If it just matches the 60 phis its rider, the reading is 65. 
If the blood is paler than this, yet darker than 60, it is about 62|-. 
An error of about 2 degrees is obviously inevitable. 

IV. Use of V. FleischVs Hcemometer. 

(a) Fill on one side of the metallic cell (a, Fig. 17) about one- 
quarter full of distilled water. Put the end of the little pipette {B) 
horizontally into the side of the blood drop, which will at once fill 




Fig. 16. — J., Colored Fig. 17.— v. FleiscWs Haemometer. a, Partition into which blood 
glass ; B, capillary is put ; a', partition into which water is put ; (?, mixing cell ; 
pipette. K, colored glass slip (see Fig. 16, A); P, P, metal frame on 

which scale is marked ; i?, S, reflector ; T, screw which moves 

the frame, P, P. 

the tube by capillary attraction. Quickly wipe away any blood 
that may be on the outside of the pi]3ette. Then put it into the 
water contained in one of the partitions of the metallic cell and rat- 
tle it quickly back and forth, so that the water may be forced in 
first at one end and then at the other. 

(b) After this the expulsion of the blood may be completed by 
forcing water from a medicine dropper through the capillary pipette 
and into the compartment where the mixuig has been begun. Using 
the metal handle of the pipette, mix the blood and water in every 
part of the compartment. Then fill both compartments of the cell 
to the brim with distilled water^ and adjust the compartment con- 



38 



CLINICAL BLOOD EXAMINATION. 



taiiiiiig the clear water so that it comes over the slip of colored 
glass, while through the compartment containing the blood light 
thrown upward by the reflector below passes directly to the eye. 
Turn the thumb screw (see Fig. 17, T) back and forth until the 
color of the glass is the same as that of the blood, and read off the 

number on the scale which 
corresponds to that color. 
This gives the percentage of 
haemoglobin, 100 being the 
color of normal blood for men 
and 80-90 for women. 

(c ) Matching the colors is 
not at all easy at best, but 
may be somewhat aided by 
observing the following pre- 
cautions : 

1. Do not stand {or sit) 
facing the light, hut sidewai/s 
{i.e., at A or B, never at C, 
Fig. 18). By sitting as in 
Fig. 18, A or B, we get the 
compartments whose colors 
we are to match, on the right 
are equally sensitive in most 




B 



Fig. 18.— _L, Light; A and B, right positions for 
observer ; C, wrong position for observer ; D, cell 
in place. 



and left halves of the retina, which 
persons. 

2. Use as little light as j^ossible, and always less light for a blood 
havmg a low haemoglobin percentage than for one nearer the normal. 

3. Boll a 2nece of paj^er { ^jreferahly black) into a tube of such 
size that it will fit over the metallic cell (D, Fig. 18), and rest on 
the platform of the instrument. Looking through this with one eye 
we can judge the color more accuratelj^ 

4. Use first one eye and then the other, and never look more than 
a few seconds at a time. 

5. Move the thumb screic with short, quick turns rather than 
slowly and gradually, for sudden color changes affect the retina 
more than gradual ones. 

6. If the preluninary reading shows one of thirty per cent or 
less, two or three pipettes full of blood should be used and the 
reading divided by 2 or 3. A considerable error can thus be 
avoided. 



SPECIFIC GRAVITY. 



39 



Necessary Errors. 

A considerable error is absolutely necessary, inasmuch as the bit 
of colored glass to be seen at any one time through the aperture of 
the instrument is not (like the blood) all of one 
tint, but includes a variation of twenty per cent 
in color, i.e., if the glass appearing at one end 
of the aperture is opposite 50 on the scale, that 
seen at the other end of the aperture will either 
be at 30 or at 70. This difficulty is somewhat 
lessened by shutting off from view all but a 
small section of both compartments with a bit of 
black cardboard or metal in which a slit is cut 
as in Fig. 19. The slit is put at right angles 
to the partition which divides the cell so that fig. 19.— shield for use 
the blood tint is seen at h and the glass tint at w. ^' Fieischi's Has- 

^ _ mometer. 
Many persons are not sensitive enough to 

colors to attain any reasonable degree of accuracy with the instru- 
ment, and there is moreover a very considerable difference be- 
tween different instruments in respect to the color of the glass 
slip.' 

All these difficulties render the instrument an unsatisfactory one 
in many ways. Its bulk and expense are also considerable and in 
my opinion its use should be entirely abandoned in favor of Tall- 
qvist's or Dare's instrument. 




Estimating the Specific Gravity of the Blood. 

The simplest and most available method for clinical use is that 
of Hammerschlag,^ a modification of Eoy's^ method. Chloroform 
is heavier than blood ; benzol is lighter. Mix in a urinometer glass 
such quantities of the two that the specific gravity taken by an or- 
dinary urinometer is about 1059, i.e., that of normal blood. Punc- 
ture the ear, draw a drop of blood into the tube of a Thoma-Zeiss 
pipette, a small medicine dropper, or any other capillary tube, and 
blow it out again into the chloroform-benzol mixture. The blood 
does not mix at all with these liquids but floats like a red bead. If 

' Old instruments read lower than those recently manufactured. 
^Wien. khn. Woehenschrift, iii., 1018, 1890. 
2 Proceedings of Physiological Society, 1884. 



40 



CLINICAL BLOOD EXAMINATION. 



it sinks to the bottom add chloroform, if it rises to the top add 
benzol, until finally the drop remains stationary in the body of the 
liquid, showing that its specific gravity is just that of the surround- 
ing mixture. Then take the specific gravity of the liquid, as we do 
of urine, and you have the specific gravity of the drop that floated 
in it. The following precautions are needed : 

1. Have the inside of the urinometer glass perfectly dry and 
clean ; otherwise the drop of blood may cling to it and flatten out 
against it. 

2. It is usually well to have more than one drop of blood in the 
glass in case any mishap occurs with the first one. 

3. Add the chloroform and benzol a few droits at a time, and 
after each addition stir the whole mixture thoroughly with a glass 
rod. 

4. If we have reason to suppose the blood will be lighter than 
normal (i.e.y if the hsemoglobin is probably low, vide supra), it 
saves time to start with a lighter mixture of chloroform and 
benzol. 

5. Avoid having any air within the blood drop. This can gen- 
erally be seen either in the capillary tube or after the dro^) is in the 
mixture. It is safer to take the middle portion of the blood drawn 
into the capillary tube, as both the first and the last portions of the 
column are more apt to have air iiL them. 

6. The whole process should be done as quickly as possible, else 
the chloroform or benzol may evaporate or work into the blood drop 
and so affect its weight. 

It is better to have a urinometer with a scale running as high 
as 1070, but this is not essential, for the clinically important spe- 
cific gravities are low, not high. 

The importance of the specific gravity of the blood, as hinted 
above, is not so much for itself, but because it runs parallel to the 
percentage of hsemoglobin and gives a figure from which the latter 
can be computed. 

The specific gravity of the blood plasma varies very little (ex- 
cept in dropsy from any cause), and in the corpuscles themselves 
the variable element is the haemoglobin.' Consequently in most 
non-dropsical patients the specific gravity of the whole blood varies 
directly as the hsemoglobin. The following exceptions to this rule 
must be borne in mind. 

^Except in dropsy in wliicli the corpuscles themselves may get water-soaked. 



SPECIFIC GRAVITY. 



41 



1. In leukaemia the specific gravity is relatively higher than the 
haemoglobin on account of the weight of the leucocytes. 

2. In pernicious anaemia with high color index (see blow) the 
haemoglobin is about two per cent higher than we should gauge it 
to be judging by the specific gravity. 

To estimate the percentage of haemoglobin from the specific 
gravity, one of the following tables may be used, modified from 
Schmaltz, "Pathologie des Blutes," etc., Leipsic, 1896, using a 
direct weighing method. Apparently a degree of specific gravity 
means much more at the top of the scale (i.e.y 6.6 per cent) than at 
the bottom (If per cent). This table has been verified by the re- 
search of Yarrow (^University Med. Mag., 1899) through comparison 
with a standard solution of 13.77 gm. of prepared haemoglobin in 
normal salt solution (up to 100 gm.). It appears to be very ac- 
curate. 



Spec. Grav. 


Haemoglobin. 


Spec. Grav. 


Hsemoglobin. 


1030 = 


20 per cent. ± 


1049 = 


60 per cent, d 


1035 = 


30 


1051 = 


65 


1038 


35 


1052 = 


70 


Kill = 


40 


1053.5 ---= 


75 


1042.5 = 


45 


1056 = 


80 


1045.5 = 


50 


1057.5 = 


90 


1048 = 


55 


1059 = 


100 



Study of the Finer Structures of the Blood. 

The study of dried and stained specimens with the help of the 
aniline dyes gives us much of interest and importance in regard to 
the. blood. More can be told about a given case by the study of a 
dried and stained cover-glass specimen than by any other single 
method. 

Freparcdion of Cover- Glass Specimens. 

(a) Covers carefully cleaned and polished are arranged at the 
bedside in such position that we can quickly pick them up without 
touching their surfaces (see Fig. 1).^ The ear is punctured in the 
usual way, and one of the cover-glasses touched to the summit of 
the drop as soon as it emerges. This cover-glass is then let fall 

^ I often poise tliem on corks so that their corners are readily accessible to 
the fingers. The process of making blood films is far easier if another person 
prepares the drop for us so that we can stand ready with a cover-glass in each 
hand to catch the drop as soon as it emerges. 



42 



CLINICAL BLOOD EXAMINATION. 



upon another in sucli a way that their corners do not coincide (Fig. 
20). If the covers are clean the drop spreads at once over their 
whole surface ; as soon as it stops spreading, slide off the top one 
without lifting them aijart, but exactly in the plane of their surfaces. 
Have a gas or alcohol flame at hand and dry instantly if you want 
to get the very best specimens ; but this is not at all necessary for 
most clinical purposes. The under cover-glass is always better 
spread than the uijx^er. 

The above method needs a good deal of practice, {b) An easier 
way of preparing blood films is as follows : 

Put a moderate sized drop of blood on a glass slide (not a cover- 
glass) near one end. Hold another slide (or a cover-glass) against 




Fig. 20. Fig. 31.— Spreading Blood on a Glass Slide. 

the first in the position shown in Fig. 21. Move the slide along in 
the direction shown by the arrow so as to spread the blood drop 
over the whole length of the glass as thinly as possible. The 
quicker the whole process is performed the better will be the re- 
sults. After drying the film in the air it can be fixed and stained 
as below described 

(c) Howard and Pakes' use the following modification of Man- 
son's method: Blood is collected on a bit of paper and with this is 
spread along the surface of a slide or of a large (li in. by f in.) 
cover-glass. 

" We have tried various kinds of tissue paper and have finally 
accepted cigarette paper as the most convenient. There are two 
small points to be noticed. Firstly, the edge used must be the 
original machine-cut edge ; and secondly, it must be that which is 
parallel to the ribs. The best papers are the Tarlene, or the Zig- 
zag, not the familiar A. G. papers. Strips are cut across the ribs 
so that each is about half an inch wide and as long as the original 
' Journal of Tropical Medicine, February, 1899. 



SPECIFIC GRAVITY. 



43 



cigarette paper is wide. Should cigarette papers not be at hand, 
ordinary note paper may be used, but it is not nearly so good. 

In making the film the strip is held between the thumb and first 
finger and is lowered till the under siu^face adjacent to the machine- 
cut edge just touches the drop of blood as it rests on the skin, and 
then by a slight lateral movement the drop is converted into a streak, 




Fig. 32. 

as in the diagram. This end of the strip is at once laid blood down- 
ward on one end of the cover-sli|), the other end being still held, 
and the blood havmg been allowed to spread out between the paj)er 
and the cover-slip, the paper is slowly drawn along the sli^^ toward 
the other end. A fresh strip of paper should be used for each 
film " 

Fixing tlie Films. 

These films have now to be fixed, either by heat or by half an 
hour's immersion in absolute alcohol and ether (equal parts), or by 
the same mixture (30 c.c. each) plus five drops of a saturated alco- 
holic solution of corrosive sublimate (five minutes' immersion) , by 
chromic acid two per cent, or by exposure to the vapor of forty -five 
per cent formaldehyde. I have used all these methods, but found 
none of them to compare favorably with the method of heat fixation 
when we wish to study the leucocytes or the nuclei of any cell. 

When we wish to see chiefly the changes in the red cells (as in 
studying the malarial organism, nucleated red corpuscles, degener- 
ative changes, etc.), the alcohol-and-ether method is good. But 
when, as m the majority of cases, it is the white cells in which our 
interest centres, the use of heat is very greatly to be preferred. 
Heat serves not simply to fix the cells on the glass and to prevent 
degenerative changes, but also to modify and greatly improve the 
staining power of the cell when Ehrlich's triacid stain is used. 

The method of fixation by alcohol and ether needs little com- 
ment, the cover-glasses being simply left in the mixture half an 
hour or as much longer as is convenient. Half an hour is enough. 



44 



CLINICAL BLOOD EXAMINATION. 



In most cases we use dry lieat. The best way to do this is in a 
dry -heat sterilizer at a temperature of 115°-155° C, according to 
the size and construction of the oven and the kind of stain used. 
The temperature must be watched very closely, and as soon as it 
reaches the desired point the heat should be removed. Gradual 
heating and gradual cooling are best. If we cannot easily get access 
to such an instrument, we can manage very well with any small iron 
or copper box having a door or lid and a hole for a cork which is 
perforated for the thermometer bulb. This supported over a gas or 
alcohol flame does very well. It needs about live minutes to get the 
temperature to 150° C, and as soon as it gets there the specimens 
should be taken out. The thermometer bulb must rest as near as 
possible to the blood films without actually touching them. Ovens 
vary a good deal in the amount of heat actually conveyed to the 
film with a given reading on the thermometer. Some heat the film 
as much with a reading of 115° C. as others with one of 150^ C. The 
proper temperature must be ascertained once for all by experiment 
with each oven. The same end can be accomplished soniewhat less 
accurately with a strip of copper supported over a Bunsen burner or 
a small gas or oil stove. The copper plate should be about a foot 
long and two or three inches wide. Such a plate supported on an 
iron tripod over a flame gets, after a few minutes, to have a fixed 
temperature at any given distance from the flame, the heat passing 
off at the end of the plate as fast as it comes, and so not accumu- 
lating. On this plate find the boiling point of water by dropping 
small drops of water on it, and put the cover-glasses at this point 
face doivnward. They may be left there for from fifteen minutes 
to as long as you please; but with the stain which I have used, fif- 
teen minutes' heating gives as good results as a longer period, and 
excellent specimens can often be made with five minutes' heating. ^ 
After allowing the specimens to cool they are ready for staining. 
A very fair oven can be made out of a five-ounce quinine can, by 

1 With a little practice one can learn to make excellent specimens b}' sim- 
ply passing the cover-glass through a Bunsen or alcohol tiame about twenty 
times very rapidly. The rate of speed must be learned by experiment, i.e., 
such a speed and sucli a number of exposures to the flame as turns out to give 
on staining a bright yelloiD color to the red corpuscles {never red or brown or 
gray), a good definition to the blue- stained nuclei and to the violet or pink 
granules of the polynuclear leucocytes. These are the essentials of a well- 
stained specimen, and they depend {a) on the heating, {b) on the make of stain, 
but onl}' slightly on the length of staining {xide infra). 



STAINING. 



45 



boring small holes in opposite sides and drawing through them cop- 
per wires on which to support a piece of wire netting to serve as a 
shelf for the blood films. A circular hole iDunched in the top of 
the can admits a perforated cork through which a thermometer 
registering 200° C. is passed. The whole is heated by a Bunsen 
burner. 

Staixing. 

For all details of structure the Ehrlich tricolor mixture or one of 
the numerous modifications of it is most convenient. The most use- 



ful and easily obtained of these is made by mixing : 

Saturated watery solution of orange G 6 c.c. 

" " " " add fuchsin 4 " 

To these add a few drops at a time, shaking between each addition 

Saturated watery solution of methyl green 6.6 c.c. 

Then add : 

Glycerin 5 c.c. 

Absolute alcohol 10 " 

Water 15 " 



Shake well for one to two minutes. Let stand twenty-four hours. 
Do not filter.' G-. Grubler's colors are best. 

I have used only this stain for the past six years, and have 
never seen any other which compares with it in brilliancy and gen- 
eral usefulness. 

The staining process is remarkably simple. A drop of the stain 
is simply spread over the surface of the cover-glass specimen with 
a glass rod and Avashed off again with water after five minutes or 
as much longer as is convenient. With th is mixture it is imjjossible 
to overstain. If the specimen look too dark (brown or red instead 
of orange-yellow) it is not because of overstaining, but because of 
vnderheatinrj. It needs a good deal of heat to bring out the full 
brilliancy of the three colors, and the 100°-120" C. usually recom- 
mended for heating is entirely insufficient with this stain unless 
continued for a long time. 

If overheated the specimen looks pale lemon yellow to the naked 
eye, and under the microscope everything is blurred and dim. Dr. 

- An absolutely reliable triple stain from Ehrlich 's latest formula can be 
had of IValter Dodd, apothecary to the Massachusetts General Hospital. A 
65-cent bottle will stain several thousand specimens. 



46 



CLINICAL BLOOD EXAMINATION. 



H. P. Hewes has suggested the following method of improvmg the 
definition of the nuclei. After washing off the triple stain he pours 
upon the film a saturated aqueous solution of methylene blue and 
after a second or two (not more) washes it off again. The specmien 
is then dried in blotting paper and mounted in balsam. 

I am convinced that any one who has once seen how much is 
brought out by a good make of triple stain followed by methylene 
blue for a second or two will never use any other for clinical pur- 
poses. The blue counterstain also brings out clearly the outlines of 
the malarial parasite against the yellow of the red corpuscle. Eosin 
(one-per-cent alcoholic solution) followed after a few minutes by 
Delafield'S hsematoxylon for one minute, or methyl blue one-half 
minute, gives a very striking contrast stain, but does not bring out 
the points most essential in clinical blood work. To "control" 
Ehrlich's triple stain with eosin-lisematoxylon or eosin-methyl blue 
is like controlling a chronometer with a fifty-cent clock. The latter 
stains are very valuable for the study of the finer structure of nuclei, 
for karyokinetic figures and basophilic granules, but not for diag- 
nosis. 

After staining and washing in water, the covers are dried be- 
tween layers of filter paper and mounted in Canada balsam, ready 
for examination with the one-twelfth oil-immersion lens, with wide- 
open diaphragm.' 

Differential Counting. 

The only procedure in the microscopic examination of such 
specimens which needs any description is that of making the so- 
called "differential count" of the leucocytes {i.e., determining wha"*- 
percentage of the leucocytes present belongs to each of the sub- varie- 
ties as described on pp. 62-67). To do this accurately we should 
examine at least five hundred leucocytes — the examination being 
simply the classification of them under their different sub-varieties. 
A movable stage is very convenient though not essential for this 
purpose. With such a stage the technique is simply to start with 
the lens in, say, the upper left-hand corner of the blood film and, by 

^ Of late I have used dry lenses a great deal — the 7 or even the 5 of Leitz — 
on account of their larger field. Most cells can be easily recognized with this 
power after we have well learned their looks by earher study of specimens 
with the immersion lens. If in doubt about any cell, it is easy to pull out 
the tube of the microscope or put on the immersion lens. 



BACTERIOLOGICAL EXAMINATION. 



47 



turning the screw of the mechanical stage, move the preparation 
slowly past the eye until the upper right-hand corner is reached. 
During this process as the cells appear in the field they are checked 
off. and put down under one or another heading. Then move the 
stage so that the lens is just one field's diameter nearer the right 
hand lower corner of the preparation, and go back again from right 
to left, following the serpentine track indicated above in Fig. 7. To 
move the lens just one field's diameter we have only to fix the eye 
on a cell at the extreme edge of the field, and then move the stage 
till that cell disappears out of sight on the opposite side of the field. 
Thus we avoid any chance of counting the same cells twice, and yet 
are sure not to miss seeing any. 

As we go back and forth in this way, we notice chiefly the white 
cells of course, but yet keep our eyes open for any unusual appear- 
ances in the red cells. Usually these move by in a monotonous 
stream, one looking much like another, but in pathological blood we 
must always be on the lookout for nucleated red cells, degenerative 
changes, and variations in size and shape. In malarial cases of 
course our scrutiny is directed chiefly upon the red cells. 

If we have not the help of a movable stage we try to do the same 
thing moving the slide with the fingers. With moderate care there 
is no danger of counting the same cells twice, but we cannot help 
missing a good many altogether, so that although accurate the proc- 
ess takes longer. 

When leucocytosis is present, at least one thousand leucocytes 
can be found in a single well-spread seven-eighth-inch cover-glass 
specimen. In normal blood we may need to go through two or 
three covers. 

Bacteriological Examination. 

Blood obtained by the ordinary method of puncture is not fit for 
bacteriological examination.^ The following is the better way: 

Sterilize the skin over the flexor surface of the bend of the elbow, 
and wash off thoroughly the agents used for sterilization with boiled 
water or boiled normal salt solution. Have an assistant grasp the 
upper arm so as to prevent the venous return and distend the large 
veins at the elbow. Into the most prominent of these plunge a 
sterilized hollow needle connected with the bulb of a sterilized 

^ See Kuhnau's comparative experiments in Deut. med. Woch., 1897, No. 25 



48 



CLINICAL BLOOD EXAMINATION. 



syringe. All traces of antiseptics must be carefully washed out of 
the needle and the syringe bulb before using. 

When the needle penetrates the wall of the vein the blood 
usually begins to flow into the bulb of. the syringe, and this is 
hastened by gently withdrawing the piston until 1-2 c.c. of blood 
are in the bulb. Then withdraw the needle, press a pad of steril- 
ized gauze over the wound, and expel the blood before it coagulates 
into a blood-serum culture tube so that it shall run down over the 
whole surface of the " slant " and collect a little at the bottom. 
The tubes are then put at once into the thermostat. 

In examining for the gonococcus the blood is to be mixed with 
equal parts of agar-agar (previously melted down so as to be mix- 
able but not hot enough to kill the organisms) , and then plated. 

The further examination of cultures falls outside the scope of 
this book. 

In the above procedure the only difficulties are : 1. Sometimes it 
is hard to find a vein and to get the needle into it. 2. Occasionally 
we get the needle entirely through the vessel into the tissues on the 
other side. 

If the blood does not flow readily into the bulb one of these two 
mistakes is usually the cause, but occasionally in those whose ves- 
sels are very small or whose circulation is very feeble (as in the 
moribund) it is very hard to get the requisite amount of blood. 
Only practice helps us to avoid these difficulties. 

The procedure causes hardly more pain than the use of an ordi- 
nary subcutaneous injection ; the process of sterilization is usually 
more irksome to the patient than the puncture. 

Bleeding is trifling, and within twenty-four hours there is usually 
no trace of the puncture left. A sterilized dressing with moderate 
pressure should be applied. 

Estimation of the Time and of the Completeness hf Coagulation. 

In certain conditions, particularly in acute exanthemata, clotting 
is slow or fails to occur. This is still more marked in the various 
forms of the hsemorrhagic diathesis. In obstruction in the biliary 
tract with or without jaundice, clotting may be greatly delayed, 
and this fact is of great importance to the surgeon with reference 
to the question of operation. 

Hayem has called attention to the fact that in purpura haemor- 
rhagica the blood clot may form, but fail completely to retract. 



OTHER METHODS. 



49 



He further believes that the blood of pernicious ansemia may be 
distinguished from specimens obtained in cases of secondary anaemia 
by the fact that in pernicious anaemia there is an incomplete for- 
mation of serum. 

In both these conditions the blood plates are greatly diminished. 
He has found similar changes in some other cachectic conditions. 

The importance of these facts in the prognosis of purpura may 
be considerable — the severer forms being thus distinguishable from 
the milder types (according to Hayem) even during the remissions 
or non-hsemorrhagic stages of the disease. 

^ For the estimation of coagulation time the simple little instru- 
ment devised by Wright is sufficient. This consists simply of a set 
of from six to twelve capillary tubes of about the same calibre (.01 
to .0125 inch) into each of which a blood column about two inches 
long is aspirated. The tubes are then set perpendicularly in a rack 
and at regular intervals the condition of the blood is tested by blow- 
ing into one of the tubes. When coagulation occurs, the tubes are 
found to be blocked with clot. 

Normally coagulation occurs in these tubes in about three min- 
utes. In disease, especially in cases with biliary obstruction, coag- 
ulation may not occur until ten to fifteen minutes have elapsed. 

Other Methods of Blood Examination. 

It is perhaps worth while briefly to mention some other methods 
of blood examination of which no account will be given. 

1. Determination of the alkalinity of the blood. No accurate 
and clinically available method has yet been devised. Despite the 
interesting work of Kraus, Caro, Lowy, Biernacki, v. Limbeck, and 
others, I am still unable to get hold of any clinically valuable in- 
formation given by the determination of alkalinity. 

2. Resistance of the red corpuscles to the influence of distilled' 
water. As is well known, Avater breaks up red cells, but if we add 
a certain amount of alkali, say NaCl, the cells remain uninjured. 
The amount of NaCl which has to be added to prevent the destruc- 
tion of red cells is from 0.44 to 0.48 per cent. Under certain path- 
ological conditions it needs either more or less of the salt to keep the 
cells intact, i.e., they possess an increased or diminished power of 
resistance against the destroying influences of distilled water. The 
degree of concentration necessary to maintain red corpuscles intact 

4 



50 



CLINICAL BLOOD EXAMINATION. 



is kno^vn as the isotonic coefficient of the blood as stated iii terms 
of a given salt; 0.44-0.48 is thus the coefficient of normal blood 
corpuscles in XaCl. 

The resistance of the blood cells to the influence of electricity, 
heat, and mechanical pressure has also been im^stigated in A^arious 
conditions of health and disease. \Yelch has suggested a possible 
clhiical application of these facts. There is much, he says, for the 
view that the number of blood plates is an index of lowered resist- 
ance in the red cells. When resistance is lowered and blood plates 
increase, intravascular thrombosis — so much cbeaded m chlorosis, 
so eagerly desired in aneurisms, is more apt to occur. 

3. The amount of solids in a given quantity of blood can be de- 
termined by weighing a given amount of blood before and after six 
hours' drying at 65° C. Inasmuch as the haemoglobin percentage 
aiid the specific gravity run practically parallel with the amount of 
solids this method has no considerable clinical value. 



PART II. 



PHYSIOLOGY OF THE BLOOD. 

CHAPTER IV. 

OxLY such portions of our knowledge of blood physiology will 
be ent3red upon here as are necessary for an understanding of the 
small group of pathological changes which can be profitably inves- 
tigated by clinicians. This limits us for the present to the mor- 
pliolofjy of the blood, its coloring 'matter, and its density under 
physiological conditions. 

Appearance of Fresh Normal Blood. 

A drop of normal blood spread between slide and cover-glass 
as directed on page 9 and exammed immediately with a one-twelfth 
immersion lens, amazes us first of all by the entire absence of any 
red color. All we see is a colorless liquid in which masses of very 
pale greenish-yellow discs are floating or lymg. 

/. Red Corpuscles. 

(cc) If the blood is spread thickly the blood discs are often ar- 
ranged in the form of rouleaux (Fig. 23). The entire absence of 
this tendency to rouleaux formation is pathological. Ic is to be 
avoided, of course, as far as possible, as it gives us only the thm 
edges of the corpuscles to look at, and covers up much that we need 
to study. Thin spreading of the blood is therefore important. 

(h) There is not much variation from the accurately round shape 
of each corpuscle in normal blood, except where one is indented by 
another. As they are moved about by the currents set in motion 
by the gradual drying up of the plasma and strike against each 
other, they bend, double up, or indent each other, like bags of jelly, 
but yet always have a strong tendency to return elastically to their 
round outline when free from pressure. Thus a corpuscle passing 
through a narrow passage between two leucocytes will be flattened 



52 



CLINICAL BLOOD EXAMINATION. 



out like a worm ; but as soon as it emerges on the other side, it will 
be as round as before. 

(c) The central hkoncavity of the cell, being thinner than the 
rim, is lighter colored. Just how much lighter should be learned 
by practice so that we may detect any abnormal pallor of the cor- 
2)uscles due to lack of haemoglobin. Pallor is to be seen mostly in 
the centre of the cell, which in extreme cases seems almost trans- 
parent. This is not to be confounded with the highly refractile, 
glistening- white centres seen as a mark of necrosis as soon as the 
blood begins to dij up. A fuller description of these appearances 
is given in the chapter on the malarial organisms, with some forms 
of which they may be confounded. 

(d) Slight variations in size are present among normal red discs, 
and here again only practice can teach us where the normal limits 
end and the pathological begin. Cells may be (pathologically) all 
undersized or all oversized, so that a standard of comparison is not 
always to be looked for in the preparation itself. 

(e) If we focus carefully on a single red cell, we can usually 
make out a fine, wavy, so-called niohcuhir motion in it. This is 
quite different from the active amoeboid movements observed in 
dying cells, and from the rapid dancing of malarial pigment. 

(/) The familiar appearance of spines all over the cells usu- 
ally called " crenation " need not be described here (see Fig. 26, 
P-84). 

But it is the very earliest beginning of crenation that leads to 
mistakes, as when only one projection has been developed and that 
points toward the eye, so that a bright spot in the corpuscle is all 
we see. 

(r/) Unless we disinfect the skin before puncturing we must be 
prepared to find in fresh preparations (a) oil drops ;^ (h) epithelium ; 
(c) particles of " dirt " ; (d) small colorless motile organisms about 
1 fj. in diameter (Mliller's " Haemoconien " — see p. 60). 

(Ii) We may make a rough estimate of the numher of red cells 
present if we take care to spread the drop of the same thickness 
each time. The eye gets used to the ordinary look of a well-filled 
field of corpuscles and notices a look of thinness if any considerable 
ansemia is present. 

(/) The degenerative changes to be seen in normal blood after 
long exposure to the air. which can get in between slide and cover, 
'In some conditions the blood really contains fat {ride infra, "Lipfemia "). 



PHYSIOLOGY OF THE BLOOD. 



53 



are described in detail later on. In pathological blood we may find 
these as soon as the blood is drawn. 

//. White Cells. 

(a) The iv kite or colorless cells are but little different from the red 
in color, the latter being so nearly colorless. We first notice them 
either by their amoeboid movements, or because they are not moved 
by the plasma currents, but stand like a rock round the sides of 
which the current of red cells is broken. They are slightly larger 
in most instances than the red cells ; but this difference shows less 
in the fresh specimens where the leucocyte keeps its spherical shape 
than in the dried and stained preparations, where it is usually some- 
what flattened. Their shape is very irregular and their edges often 
look tattered. 

In some leucocytes the amoeboid motions are entirely absent. 
These are the smallest cells, and in them a single nucleus filling 
most of the cell can often be seen. They are much more nearly 
spherical and less irregular than the amoeboid cells. 

The large amoeboid leucocytes are more or less granular, and in 
certain lights these granules look quite dark and are sometimes 
mistaken for bits of malarial pigment. This is especially true of 
the coarse granular cells seen occasionally; staining shows these 
large granules much more distinctly (= eosinophile — see below, p. 
65) ; cells of this type are the most actively amoeboid of all. 

(h) The most important point in connection with the leucocytes 
is their ratio to the red cells. This is estimated in fresh specimens 
not by any actual counting but by reference to a standard fixed in 
the mind by study of normal specimens, and any considerable 
increase of the white cells would be noticed at once. Naturally we 
must not judge from any one part of the slide, as the distribution 
of the leucocytes may be unequal in different parts of it. 

III. Blood Plates.' 

Unless the number of these elements is increased by some path- 
ological influence, we seldom notice them at all in normal blood. 
This may be because we do not work quickly enough in preparing 
our specimen. Hayem recommends that the cover-glass be laid 

^ It is probable that the elements included under this heading comprise 
several different things. It is beyond the plan of this book to discuss their 
origin and significance, since they possess at present no clinical value. 



54 



CLINICAL BLOOD EXAMINATION. 



upon the slide before the puncture is made ; as soon as the drop 
emerges it is allowed to run in between slide and cover by capillary 
attraction, thus avoiding contact with the air.^ The blood plates 
are irregularly shaped, very cohesive elements, about one-half the 
diameter of a blood disc, usually seen clinging together in masses 
like zoogloea. They are colorless and not amoeboid and look like 
debris. 

IV. Fibrin Xetwork. 

After a specimen of fresh blood has stood for some time exposed 
to as much air as can creep in between slide and cover-glass, we 
begin to notice a network of fine straight lines in the spaces be- 
tween the corpuscles. Here and there these filaments seem to 




Fig. 23.— Rouleaux Formation and Fibrin Network of Normal Blood. 



radiate from a centre where irregular, colorless masses, apparently 
blood plates, are to be seen (Fig. 23). 

No stain is needed to demonstrate these fibrin threads, but a 

^ This is a very satisfactory waj' if we wish to see the corpuscles as fresh 
and unspoiled as we can. Put a cover-glass on a slide so that the edge of one 
corresponds with the edge of the other, and, holding them in this position 
with finger and thumb, put their superimposed edges into the side of the 
drop as it emerges. It will run in between them by capillary attraction. The 
blood plates can be stained with eosin, and in the eosin-htematoxylon stain 
are easily seen and their number approximately estimated. 



PHYSIOLOGY OF THE BLOOD. 



55 



small-aperture diaphragm and very little light make them plainer. 
Their only importance is that under certain pathological conditions 
the fibrin network is very much increased and helps us in the diag - 
nosis (Fig, 24). Hence it is of importance to be familiar with the 




Fig. 24.— Increased Thickness of Fibrin Network. 



ordinary closeness of the network in normal blood as a standard of 
comparison. 

For an account of the conditions of its increase see Chapter IX., 
page 121. 

Average Diameter of Red Cells. 

The blood under normal conditions shows considerable variations 
in the size of its corpuscles in the fresh state as well as in stained 
specimens.^ 

' A method of measuring, approximate!}' accurate, and easil}' applicable 
in clinical work is the following : 

Using a camera lucida, trace on paper the divisions of a fine stage micro- 
meter as seen under a one-twelfth oil immersion lens ; such micrometers are 
usually ruled to one one-hundredth of a millimetre. Approximate accuracy 
in our tracing can be obtained if the process is repeated till the divisions 
marked in successive drawings correspond accurately one with another. Care 
must be taken that the paper is flat upon the table beside the microscope, and 
not raised on a block or otherwise ; also that the part of the paper on which 
we draw should be perpendicularly under the centre of the mirror and not 
off to one side. When a drawing has been made with these precautions, we 
have only to divide the space between each of the lines in our drawing into 



56 



CLINICAL BLOOD EXAMINATION. 



The following table (v. Limbeck) shows the results of various 



observers. 

Normal Limits. Average Diameter. 

Welcker diameter = 4.5-9.5 7 ,u 

Valentin 7 // 

Malinin 7.7,// 

Hay em diameter = 6-8.8 . 7.5 

Mallassez 7.6// 

Laaclie diameter = 6-9 . . 8.5 /x 

Bizzozero 7.075// 

Gram diameter = 6. 7-9. 3 // 7. 850 // 



Average = 7.5 // 

These differences depend partly on differences in the method of 
measuring (wet or dry), and partly on the fact that the age and 
conditions of nutrition in the persons selected make a difference. 
In the new-born, and to some extent throughout childhood, the 
normal limits of variations are wider than in adults (3. 3-10. 5 /j, 
Hayem). Sex appears to have no constant influence. 

Gram^ noted that the measurements published bj observers liv- 
ing in southern Europe are smaller than those of northern Europe 
(Italians 7-7.5, Germans 7.8, Norwegians 8.5). 

The majority of any individual's red cells are certainly about 
7. 5, a in diameter, and this may accordingly he taken as our standard 
(Hayem counts twelve per cent under 6.6/^., twelve per cent over 
8/-/, the rest 7. 5, a). 

ISToRMAL Number of the Red Cells. 

1. At the level of the sea and in adult life the normal number 
of red cells per cubic millimetre is about 5,000,000 for men and 
4,500,000 for women. This is not infrequently increased in very 
vigorous, healthy persons; 6,000,000 is by no means rare among 

ten equal parts, and we have a scale, each division of which represents 1 // as 
seen under a one-twelfth oil-immersion lens, with the length of tube of the 
particular microscope used. To use our //-scale we have only to draw with 
the camera lucida anj^ cell whose size we want to know, using alwaj's the 
same microscope, the same length of tube, and the same lenses, and having 
the drawing paper (as before) flat on the table and perpendicularly under the 
mirror. The drawing thus made is measured with the //-scale like any other 
object. 

With this method a cell can be measured in a few seconds and with sufii- 
cient accuracy {i.e., within 0.5 //). 
1 Fortschritte der Medicin, 1884. 



PHYSIOLOGY OF THE BLOOD. 



57 



healthy young men, and higher figures are seen occasionally. Thus 
Hewes' in fifty young medical students found an average of 5,809,- 
000 per cubic millimetre; of these fifteen exceeded 6,000,000, the 
highest being 6,400,000, while the lowest of the whole series was 
5,120,000. Altitude above the sea level raises the count invariably 
(see page 78) . 

2. The influence of menstruation, childhii'th, and lactation is to 
diminish the red cells temporarily, the amount of the diminution 
depending not only on the amount of blood lost but on the capacity 
of the individual organism for blood regeneration. At puberty, 
when sexual functions are being established, we exj^ect lower counts 
than after the establishment of the function. Xormal pregnancy 
does not affect the count of red cells. 

3. The count of red cells per cubic millimetre is raised by any 
cause inducing concentration of the Uood, such as profuse sweating, 
and is lowered by the temporary dilution of the blood after large 
draughts of liquid. In these changes, which are always very tran- 
sient, the haemoglobin and specific gravity in a given drop are of 
course increased with the corpuscles. 

Vasomotor influences affecting the calibre of the peripheral ves- 
sels (hot or cold baths, exercise, etc.) may temporarily concentrate 
or dilute the blood by affecting the interchange of fluid between the 
vessels and the surrounding lymph spaces. By these processes the 
blood in the peripheral vessels may show an increase or diminution 
in the cellular elements, the hsemogiobin and specific gravity cor- 
responding to the greater or less concentration of the blood at that 
point (on these points see below page 76). 

Hayem noted that in young people especially the number of red 
cells varied considerably without any notable change in conditions. 

4. Influence of Nutrition on the Xuniber of Red Cells. 

A. After a meal, especially when considerable liquid is taken, 
the blood is temporarily diluted and hence the count of red cells 
per cubic millimetre is diminished (v. Limbeck; Reinert). This is 
illustrated by the following case from v. Limbeck. 

Adult, Male, Healthy. 

Red Cells. White Cells. Hb 

11:15 A.M 5,530,000 7,660 98 per cent. 

12 M. dinner 

' Transactions of the Boston Society of Medical Science, May 18, 1897. 



58 CLINICAL BLOOD EXAMINATION. 

Red Cells. White Cells. Hb 

12:15 P.M 5,320,000 6,166 

1:15 " 5,480,000 8,500 

2:15 " 4,733,000 12,000 

3:15 " 4,872,000 14,000 89 per cent. 

4:15 " 4,720,000 10,830 89 



As the white cells rise (digestive leiicocytosis, see below, page 97) 
the red fall. 

Fasting, by concentrating the blood, temporarily increases the 
number of red cells (400,000-500,000 increase after twenty-four 
hours' fast). 

B. General Nutrition. — Lean, muscular people have on the aver- 
age more red cells per cubic millimetre than fat people (Leichten- 
stern, quoted by v. Limbeck), other things being equal.' 

As above said, fasting (by concentrating the blood), raises the 
number of red blood cells, so that it is not simply hunger that gives 
us the diminution in red cells commonly found in jjoorii/ noiirished 
2)eoph, but rather the influence of bad hygiene in the slums, etc. 

5. Seasons and the time of day seem to have no influence in 
themselves. The same is true of race and climate. The only ex- 
ception to this is reported in the work of E. Below," Avho found in 
yellow-fever districts an average count of only 4,700,000 red cells 
per cubic millimetre and the diameter of the individual cell reduced 
to 5.9/7. on the average (7.5// = normal).^ 

6. Fatigue.— TLd^j^mwot^di a loss of from 500,000 to 1,000, 000 red 
cells per cubic millimetre in the blood of a number of farmers after a 
hard summer's work, the counts made in September having been com- 
pared with those of April and always found to be lower. AThether 
fatigue is the only cause of this diminution may be doubted. 

7. Age. — In the new-born the number of red cells is very high 
for a few days (7,000,000 to 8,800,000), but falls at the end of 
seven to ten days (see page 445). 

In the very old a certain degree of anaemia is, so to speak, 
physiological ; but this, which like the plethora of the new-born is 
to be referred not to the fact of age, but to concomitant influences, 
is hj no means invariable. Schmaltz reports 6,766,000 red cells in 
a man of eighty-one and 4,816,000 in a woman of seventy-four. 

^ The influence of stasis in the obese, whose fat loads the surface of the 
heart, is to cause an apparent increase of red cells. 

'-"Deut. Tropenhygieue," Berhn, 1895. O. Coblanz. 
^ See also under Anclij'lostomiasis, p. 428. 



PHYSIOLOGY OF THE BLOOD. 



59 



Normal Number of White Cells. 

The figure usually given for adults is 7,500 per cubic millimetre. 
This varies a good deal, according to the nutrition of the individual 
(see page 95) and also at different times of the day, owing to influ- 
ences not explained. The influence of digestion will be mentioned 
later. In animals a slight shock ^ is sufiicient materially to affect 
the count of leucocytes; 5,000 to 10,500 may be called the normal 
limits. Eomberg finds 9,058 as the average count in fifty-five 
healthy young women. There is, I believe, no evidence to show 
whether or not mental disturbances (fear, rage, emotion of various 
kinds) affect their number, but my impression is that they do. 
Other causes of variation will be discussed under Leucocytosis. 

Blood Plates. 

The number of blood plates is variously estimated at from 180,- 
000 -250,000 (v. Emden) to 860,000 (Kemp and Calhoun). They 
do not contain hsemoglobin and show no signs of a nucleus. They 
are the chief constituents of white thrombi. Wherever they are 
diminished (e.^/., in haemophilia, purpura) clotting is apt to be slow, 
and there is reason to believe — 

(a) That their number is an mdex of lowered resistance of the 
red cells. 

(b) That whenever their number is much increased, thrombosis 
is likely to occur. In chlorosis, for instance, their number is in- 
creased and thrombosis is relatively common, while in pernicious 
ansemia they are diminished, and thrombosis rarely if ever occurs. 

Coagulation time outside the body depends largely on the amount 
of fibrin and is a wholly different phenomenon from intravascular 
thrombosis. This is of importance in connection with the use of 
gelatin injections to favor thrombosis in aneurisms. An increased 
rapidity of coagulation outside the body is no indication of success 
in such cases. Blood plates are increased in leukaemia and in many 
cases of grave anaemia. In the severer types of many infections 
(typhus, erysipelas, malaria) they are diminished, and in malaria 
they are sometimes wholly absent during the fever. In pneumonia 
and tuberculosis they are normal or increased. In purpura and 
haemophilia they are sometimes much diminished or absent. 

'Lowit: "Studien z. Pliysiol. und Patliol. d. Blutes," etc., Jena, 1S92. 
Fischer. 



60 



CLINICAL BLOOD EXAMINATION. 



The physiological limits of the amount of hcemorjlohin and of the 
specific cjrai-'ity have already been mentioned. Under physiological 
conditions their variations follow those of the count of red cells. 

Muller's "Blood Dust.'' 

MiiUer' has recently described under the title of " Hsemoconien," 
or blood dust, a constituent of normal and pathological blood not 
hitherto noticed. This consists of small round colorless granules 
about the size of the finest fat drops — or about \-\ }x in diameter, 
their size being very variable. They are highly refractile and have 
rapid dancing (molecular) motion, but no power of locomotion. 
They are insoluble in alcohol and ether, not stained by osmic acid, 
and take no part in the formation of fibrin. Stokes and "Wegefarth,- 
who have confirmed Mliller's observations, note that the ''blood 
dust " can be seen much more clearly by the light of a AVelsbach 
gas burner than by daylight. The latter observers present a body 
of evidence tending strongly to show that these bodies are the ex- 
truded granules of neutrophilic and eosinophilic leucocytes. Gran- 
ules apparently identical with them can be stamed in fresh specimens 
with eosin or Ehrlich's triacid stain in a way apparently like that 
of the intracellular granules.^ They are also to be seen in pus and 
in hydrocele fluid. 

Xo special diagnostic or prognostic significance has yet been at- 
tached to them, though the work of Kanthack and Stokes renders 
them of great interest with reference to the problem of immunity. 

iCentralbl. flir allg. Path., etc., viii., 1896. 

- .Johns Hopkins Hospital Bulletin, December, 1897. 

sXicholls: Phil. Med. Jour., Feb. 26, 1898. 



PLATE I. 



Fig. 1. — (a) Polymor}-)liomi clear Neutro^jliiles. Note tlie varieties in size 
and shape of granules, tlie irregular staining of the nuclei, the light space 
around them, their relatively central position in the cell. 

{h) Myelocytes. Note identity of granules with those just described; the 
even, pale stain of nuclei ; their position near the surface (edge) of the cell. 
The two cells figured indicate the usual variations in the size of the whole cell. 

(c) Small Lymphocytes. In the cell at the left note transparent protoplasm ; 
in the cell next to it note mry pale pink of protoplasm around nucleus which 
is deeply stained, especially at the periphery. The next cell has an indented 
nucleus; its protoplasm relatively distinct. The cell on the extreme right 
shows no protoplasm and is probably necrotic. In all note absence of grannies 
with this stain. With basic stains a blue network appears in the protoplasm. 

{cT) Large Lymphocytes. Note pale-stained nuclei and protoplasm, irregu- 
larity of outline ; indented nucleus in one. Every intermediate stage between 
these and the small lymphocytes occurs, and the distinction between them 
is arbitrary. 

{e) Eosinophile. Note irregular shape, loose connection of granules, their 
copper color, their uniform and relatively large size, and spherical shape. 

(/) Eosinophilic Myelocyte. Note similarity to QS) ordinary myelocytes ex- 
cept as regards granules. Color of granules may be as in (e) ordinary eosin- 
ophile. 

All the above were stained with the Ehrlich triacid stain, and drawn with 
camera lucida. Oil-immersion objective one-twelfth and ocular No. iii. (Leitz). 

Fig. 2. — Malarial Parasites in Fresh {Unstained) Blood (Tertian Forms). 
N,N, normal red corpuscles; 1, red cell containing hyaline body ; 2, 3, 4, 5, 
successive stages in the development of the parasite, showing acquisition of 
pigment; 6, 7, full-grown parasites, the corpuscle no longer visible; 8, begin- 
ning of segmentation ; 9, segmentation. In 6 and 7 note brownish blur behind 
the pigment dots. Drawn as in Fig. 1. 

Fig. 3. — Tertian Parasite Stained tcith Eosin and Methyl Blue. The re- 
mains of the corpuscle containing the parasite stain pink, the parasite blue, 
and its pigment black. The stages of growth correspond with the numbers 
attached. Note in Figs. 1, 2, 3, and 4 the shape of the parasite, shown better 
than in fresh specimen. 

[Owing to a mistake the cells in Fig. 3 are not drawn according to a single 
scale and their relative sizes must be disregarded.] 



Examination of the Blood. 

PLATE I. 



Fig. 1. Varieties of Leucocytes. 



Polymorphonuclear 
neutrophiles 




rJi'*^-.*^— Myelocytes 



Small Lymphocytes 



Large Lymphocytes 



Eosinophile — 




Eosinophilic 
Myelocyte 



Tlie Malarial Organism. 



7 %:m 



Fig. 3. 



Fig. 2. 



R. C. Cabot fee. 



Litb. A.n8t. v, K A. Kuiike, LeipziR. 



CHAPTEE Y. 



FINER STRUCTURE OF THE BLOOD. 

Appearances of Dried axd Staixed Specimexs. 

Cover-glass specimens prepared and stained as above directed 
give us more information of interest and importance than can be 
obtained from any other one method of blood examination. Ap- 
proximate ideas of the quantity of red cells, of white cells, and of 
haemoglobin can be formed, parasites and bacteria can be seen, and 
the whole mass of evidence based on the finer structure of the leu- 
cocytes can be obtained only in this way. The appearances of a 
specimen of normal blood prepared in this way are as follows : 

Red Cells. 

1. The haemoglobin stains with the orange G- of the tricolor 
mixture, and in a properly heated specimen the red cells are of a 
brilliant yellow or pale orange tmt. If overheated they have a 
feebly stained, washed-out look, while if nnderheated they are more 
or less hroivn or gray.^ 

The degree of pallor of the centres corresponding to the amount 
of haemoglobin in the corpuscle can be gauged much more accurately 
with this stain than in the fresh preparations. The color of the 
edges is not much affected by pathological changes, the centres 
being the test. But in cases with extreme poverty of haemoglobin 
the colored rim may be reduced to a mere shell and the rest may be 
almost completely colorless. The power to estimate the amount of 
coloring matter in this way can be easily acquired. 

An approximate idea of the number of red cells may be formed 
by any observer who has learned to use a uniform technique in each 
case and to spread the blood of a standard thickness. 

2. Nothing is seen of the fibrin or blood plates as a rule. In 

^ This is a fruitful source of error. Many suppose that because their speci- 
mens come out too dark they must be " burnt, " and so heat less. In fact the 
dark tint means that the specimen is not heated enough. 



62 



CLINICAL BLOOD EXAMINATION. 



normal cases the plasma does not stain at all. A certain amount 
of debris is often present, usually pink stained. 

White Corpuscles. 

3. The chief purpose and use of the "triple stain" is for distin- 
guishing the varieties of white corpuscles, and the pathological 
states of the red. About the normal red cells it gives us no in- 
formation that cannot be obtained as well by various other stains, 
but our knowledge of normal leucocytes has been immensely en- 
larged by its use. 

In normal blood, stained as above directed, we recognize the 
following varieties of white cells : 

(1) Small hjiuphocjjtes or "small hyaline forms" (Kanthack) 
(see Plate I.). These consist mostly of a round blue nucleus 
about the size of a red cell, surrounded by a thin coating of pro- 
toplasm, which is faintly stained or invisible with Ehrlich's triple 
stain, but stains dark patchy blue when Hewes' blue counterstain 
is used. 

The nucleus may be considerably smaller than a red cell. With 
ordinary triple stain it is usually pale-stained, but when a blue 
counterstain is used it stands out intense indigo color. This is one 
of the greatest merits of Hewes' after-stain. Without it the 
lymphocytes are often so pale that some of them may be overlooked 
in counting. 

The unequal staining of the protoplasm with the methylene blue 
is probably not a true granulation but a reticular structure. 

(2) With Ehrlich's triacid stain I do not find it possible to draw 
any line between this form and that now to be described, namely, 
the "large lymphocyte " or "large mononuclear cell," which is 
simply larger and paler. 

The small lymphocyte is the form most frequently seen in the 
lymph channels, in chyle, and at the periphery of the follicles of 
adenoid tissue. In the so-called "large lymphocyte " the nucleus 
occupies relatively less of the cell than in the small lymphocyte and 
stains less readily. 

In many cases we do not see in the blood any intermediate 
forms. Lymphocytes are either "small" (5-10 ij. in diameter) or 
"large" (13-15, a in diameter) (see Plate I.). 

In other cases we find every intermediate size, both of nucleus 



FINER STRUCTURE OF THE BLOOD. 



63 



and of the cells as a whole, and in such cases I am unable to make 
a division into "large" or "small," though we may be able to say 
in a general way which size predominates. The edges of the larger 
forms are often frayed and jagged, and small bits may bud off and 
circulate as free elements. This is especially frequent in lymphatic 
leuksemia. 

The theory that the "Zar</e" mononuclear cells or "large hyaline 
forms " (Kanthack) come from the spleen and the small mono- 
nuclear from the lymph glands has been abandoned on all sides of 
late years. 

The protoplasm of all lymphocytes, as has been said, is always 
hard to stain with Ehrlicli's triple stain. Sometimes it has a faint 
pinkish tinge, more frequently it is grayish or very light blue, and 
in some cases it stands out brilliantly transparent and colorless 
against the faint purplish tinge of the surrounding plasma (see 
Plate I.). When a blue after-stain is used an artificial retraction 
ring of unstained protoplasm appears around the nucleus. Some- 
times the protoplasm stains diffusely blue with basic stains and no 
network can be made out. 

I have described the lymphocytes so far as " mononuclear, " but 
it is not rare to find even very small ones (G/Jt in diameter) whose 
nucleus has a deep cut in one side or has divided into two parts. I 
believe it is commoner to find a divided nucleus in the small forms 
than in the "large lymphocytes." The inapplicability of the term 
"small mononuclear cells" or "large mononuclear cells" to this 
variety of corpuscle is evident. The distinguishing mark is not the 
single nucleus. (See also below under "Mast cells.") 

Ehrlich separates sharply under the name of " large mononuclear 
leucocytes " a group of cells closely resembling the larger forms of 
lymphocytes. Taylor and other first-class authorities agree with 
him in' this, but their descriptions include so few differentiating 
marks that I am unable to recognize them. As they make up but 
one per cent of the white corpuscles and have no clinical signifi- 
cance, I have grouped them in my counts with the large lymph- 
ocytes. I have done the same with the so-called 

3. " Transitional forms " (Ehrlich), which are no bigger than 
the larger type of Ijrmphocytes, from which they differ only in that 
they have an indentation in their nucleus — either a narrow cut or a 
bay so wide that a "horseshoe" nucleus results. This is the trans- 
itional form according to this nomenclature. There is no reason for 



64 



CLINICAL BLOOD EXAMINATION. 



calling it so, as all the forms of leucocytes are transitional, but there 
is some convenience in the name. Like most large lymphocytes it 
is pale all through — pale in both nucleus and protoplasm — and often 
escapes notice in hasty examinations. Sometimes its protoplasm is 
sparsely covered with faint neutrophilic granules. 

4. The cells known as " polynuclear " or ^o/?/??i.o?797io?i?^cZe^?r 
neutrojjhiles. These cells constitute the vast majority of those 
found in ordinary pus. The main difference between them and 
those last described is in the possession of granules, best seen when 
stained by Ehrlich's methods. The nucleus stains deeply with all 
dyes. It is very irregular in shape, being twisted about in the body 
of the cell. Here and there it may dive down so deeply beneath 
the surface of the cell that it is hidden under a thick layer of gran- 
ules, reappearing in another part of the cell so that it seems to be 
broken in two. Occasionally, no doubt, this is actually the case, 
but generally there are "underground connections" between the 
apparently separate pieces of nucleus. Now and then we see a cell 
(degenerating) where the granules have fallen away, leaving the 
nucleus like a short, thick snake, very rarely two, or like several 
sausages joined by strings. 

One never sees any two of these cells whose nuclei are of the 
same shape. Hence the term "polymorphonuclear." The wind- 
ings and twistings of the nucleus have suggested comparisons to the 
letters Z, S, E, etc. 

The granules which fill the body of the cell and in which the 

, nucleus is embedded stain best with triple stains like Ehrlich's. 
Acid stains like eosin, and basic stains like methylene blue, do not 
bring them out clearly. Hence the term "neutrophilic," which is 

. not strictly accurate ; more i)roperly they are faintly oxyphilic' and 
can be faintly stained with eosin. [Hence Kanthack and other 
English observers have called them "fine granular oxyphiles," 
while the term " coarse granular oxyphiles " is applied to the cells 
generally known as eosinophiles. These terms are in some respects 
more accurate than Ehrlich's, but are even more cumbrous than 
his.] With Ehrlich's triacid mixture the granules stain violet or 
purple, sometimes pink, their color varying apparently according to 
their age. The older the granule the pinker. The younger it is, the 
more violet affinity it has (see below, p. 69). The granules are 
very small and irregular in shape and size, contrasting with the 
^ Ehrlich's stain is really a differential acid stain and not neutral. 



FINER STRUCTURE OF THE BLOOD. 



65 





large, rouncT, " eosinophile " granules (see below). Tlie cells being 
spherical the granules lie over and around the nucleus, not simply 
at the side of it. In their interstices we sometimes seem to see a 
pinkish background of cell substance, 
trophilic " granules, which are so small 
that except with very high powers they 
look like a diffuse stain, very rarely occur 
except in cells whose nucleus has reached 
tlie polymorphous stage. Occasionally we 
seem to see mononuclear neutropMlefi^ hav- 
ing a round nucleus with neutrophilic 

granules, but careful focussing usually .^J g 

shows that the appearance of a round or 
rod-shaped nucleus is given by the tight 
coiling of the ribbon-like nucleus round 
one of its ends, or else that a horseshoe nucleus is seen from the 
point of view indicated in Fig. 25. Thus if the eye be at the point 
A the nucleus will appear of the shape indicated in B (Fig. 25). 

5. The eosinophile or " coarse granular oxyphile " cell has, like 
its predecessor, a polymorphous nucleus and granules ; but the 
nucleus is paler and more loosely connected to the granules, and the 
latter are spherical or oval, of nearly uniform size, and much larger 
than any seen in the neutrophilic cell. They have strong affinity for 
acid coloring matters (eosin, acid-fuchsin, etc.), hence their name. 
In specimens stained with eosin or eosin and methylene blue they 
are very brightly colored pink. With the triacid mixture they are 
of a copper or burnt-sienna color. Some individual granules stain 
much darker than others in the same cell. 

The eosinophiles are the most actively amoeboid of all the cor- 
puscles, and it may be for this reason that the different parts of the 
cell seem so loosely strung together. Or, if the hypothesis of Kan- 
thack aud Hardy, recently supported by Stokes, be true, their loose 
arrangement may serve to make them easily detached for bactericidal 
purposes (see above, page 60). The granules maybe all at one side 
of the cell and the nucleus on the other, an din cover-glass specimens 
we very frequently find actual separation of the two. Whether or 
not the actual separation is brought about by the technique of 
spreading the blood is unimportant, as we find such broken cells 
much more often among the eosinophiles than among any other 
variety— which argues a looser structure. 
5 



66 



CLINICAL BLOOD EXAMINATION. 



Sometimes there seem to be two or more distinct and separate 
nuclei in the cell, no ''underground connection" being traceable. 
The granules are seldom over the nucleus as we see it in cover-glass 
preparations, but cluster round it loosely. 

The cell as a whole is usually a little smaller than the '' neu- 
trophile " and more irregular in shape. In stained specimens the 
neutrophile is seldom seen with a pseudopod extended, whereas the 
eosinophile often shows it. 

The staining of the nucleus is more even as well as paler than 
that of the neutrophile, and with the Ehrlich stain often has a 
robin' s-egg tint. To sum up: 

The four varieties which we usually find among leucocytes in 
the blood are these : 

1. Small lymphocytes, or "hyaline cells." 

2. Large lymphocytes and transitional forms. 

3. Polymorphonuclear neutrophiles, or fine granular oxyphiles. 

4. Eosinophiles, or coarse granular oxyphiles. 

5. A fifth variety of leucocyte — the basophilic " mast cell " is a constituent 
of normal blood, though in very small numbers. One-half per cent is the 
maximum number in health. In leukaemia it is common, but no special sig- 
nificance is attaclied to it. Taylor found it in increased numbers in one case 
of cancer, one of gonorrhoea, one of mycosis fungoides, and two of septic bone 
disease. Canon has found a similar increase in chlorosis and some chronic skin 
diseases, and I in trichinosis. 

With Ehrlich 's stain the basophilic granules of this cell are not seen or 
appear only as clear white spots. They are best stained with thionin or tolui- 
din blue. The nucleus is polymorphous, often trilobed. 

Tekms. 

No one can feel more unsatisfied with the terminology used in 
this book than the writer. It rests partly on a theory of the origin 
of the cells ("lymphocytes partly on the properties of the nucleus 
("polymorphonuclear"), and partly on affinities for aniline dyes 
(" neutrophile " — " eosinophile ") . 

All that can be said for it is that it discards certain very mis- 
leading names like " splenocyte " (a term applied by some to the 
large lymphocytes according to the now exploded theory that they 
come from the spleen), or like "small mononuclear" to designate 
cells not rarely polynuclear. 

The cumbrous word " polymorphonuclear " is a shade better than 
"polynuclear," and that is all to be said in its favor. 



FINER STRUCTURE OF THE BLOOD. 



67 



It is greatly to be hoped that we may ere long have a new and 
improved terminology by some competent student. The English 
terms above referred to are so cumbrous that I have not as yet felt 
compelled by their slightly greater accuracy tp adopt them uncon- 
ditionally, but they certainly show a tendency in the right direc- 
tion. 

Origin of the Different Varieties. 
Two groups may be distinguished : 

' {(£) Polymorphonuclear 
neutrophiles. 
Eosinophiles. 
(c) Mast cells. 
id) Large mononuclear cells 
[ (Ehrlich)?? 
Lymphocytes of all 
sizes. 



I. The myelogenous group 
(from the bone marrow). 



II. The lymphogenous group 
(from adenoid tissue). 



Except within Group II. no transitions between the different 
varieties of circulating leucocytes are recognized. 



Normal Percentage of Each Variety. 

In the blood of healthy adults the proportions of the different 
varieties above described are the following : 



, X \ Small lymphocytes 20-30 per cent. 

Large " 4-8 

(IS) Polymorphonuclear neutrophiles 62-70 " 

(c) Eosinophiles |-4 " 

{d) "Mast cells" ^Vi 



(«) In infancy the percentage of lymphocytes is much larger 
(forty to sixty per cent) and the polymorphonuclear neutrophiles 
are only eighteen or forty per cent. 

In a variety of debilitated conditions not usually thought of as 
definite diseases, the percentage of lymphocytes is comparatively 
large and that of the polymorphonuclear cells small.' The general 
vigor and health of the individual can sometimes be estimated simply 
from the leucocytes. Persons calling themselves well, but never 
vigorous or active, may show no more than fifty per cent of poly- 
morphonuclear cells, the lymphocytes running up to forty, fifty, or 

^ This change is usually dependent on an absolute diminution in the mye- 
logenous cells. 



-68 



CLINICAL BLOOD EXAMIXATIOX. 



even seventy-five per cent. In an unmarried woman of twenty- 
nine, suffering from no discoverable organic disease, I found one 
day among 1,200 leucoc}i;es 74.9 per cent of lymphocytes with only 
25 per cent of polymorphonuclear cells. The total leucocyte count 
was 6,000 per c.mm. Two weeks later the percentages were 
normal, although no change had been observed in the patient's (de- 
bilitated) condition. She is now well and married. 

Xot all cases of debility show this change, and we are not yet 
in a position to say under just what conditions it occurs. It cer- 
tainly is not peculiar to tuberculosis as Holmes has supposed. 
Presumably the conditions are such as decrease the functional ac- 
tivity of the marrow. 

{h) Changes in the percentage of neutrophiles will be discussed 
later. 

( r) The percentage of eosmophiles often changes in a way hard to 
explain. Tlieir increase or decrease in the circulating blood does not 
follow that of the polymorphonuclear neutrophiles. in fact is often 
inversely proportional to it, and the eosinophiles maybe markedly 
increased in a blood otherwise normal, for reasons wholly unknown 
to us. 

An increase in the lyniphocytes or neutrophiles rarely occurs 
without other blood changes, and points, not to disease of one place 
or function, but to general conditions like inflammation or mahiu- 
trition. The diagnostic indications of an increase of the eosin- 
ophiles are more sj^ecific {ridf^ infra, articles "Trichinosis," '•'Asth- 
ma," "Dermatitis Herpetiformis," etc.). 

The eosmophiles and '"mast cells " may be pictured as compar- 
ative strangers, though not intruders in the circulating blood. 
They are thus intermediate between the regular inhabitants 
(hunphocytes and neutrox:)hiles) and the variety next to be 
mentioned, which are real intruders — i.e., almost never found in 
normal blood. These are the 

^Myelocytes. 

The larger portion of the leucocytes of the marrow is made up 
of mononuclear neutrophiles. a type of cell not yet described, and 
differing from any variety found in normal blood, although it has 
many points of resemblance to the polymorphonuclear neutropliile, 
and is in fact the same cell in an early stage of growth. 



FINER STRUCTURE OF THE BLOOD. 



69 



I describe it here because it is peculiar to no one disease and is 
an occasional visitor of the blood in various diseased conditions and 
in conditions on the borderland between the pathological and the 
physiological (starvation — various intoxications). 

The niyeloc}i3e (see Plate I.), like its descendant, the polymor- 
phonuclear neutrophile, is recognizable only by Ehrlich's staining 
methods. With Ehrlich's triple stain it appears as a spherical cell 
nearly tilled by a large, pale-stained nucleus immersed in neutro- 
philic granules. One sees at once how little it differs from the 
large lymphocytes (simply in having granules) and from the poly- 
morphonuclear neutrophile (only in the shape of its nucleus). I 
have called the granules neutrophilic, and this is true of the great 
majority of them in most cells. But as Ehrlich has recently 
pointed out, there is a great deal of variation in the staining affin- 
ities of different granules, side by side, in the same cell. In some 
granules (according to Ehrlich the younger ones) "there is promi- 
nent a basophil portion which becomes less and less marked as the 
cell grows older." Such granules take with Hewes' after-stain a 
bluish tint. Others near them (older?) are violet, while others 
again are nearly pink. In the polynuclear neutrophile these baso- 
phile affinities are much less marked, but even in them considerable 
differences may be made out between the tints of adjacent cells and 
of adjacent granules in the same cell. In size and shape the mye- 
locyte granules are like those of the polynuclear cell (see Plate I.). 
The nucleus, by which we chiefly distinguish the myelocyte, shows 
none of the twists and turns characteristic of the polymorpho- 
nuclear neutrophile, but is usually spherical or egg-shaped, and is 
in close contact with the cell wall for a comparatively large portion 
of its extent — i.e., if egg-shaped it is placed eccentrically. 

iSTot infrequently the nucleus shows signs of old age (vacuoles) 
or of mitosis, for occasionally we find two nuclei at the poles of the 
cell. 

Size of JI//eloc//tes. 

All the older accounts of the myelocyte speak of it as a very large 
cell, the largest variety of leucocyte ever seen in the blood. 

This is true of many of them ; diameters of 18-21 ,a are not nn- 
common, but we also find them of everi/ other size down to 10-11 ,a 
diameter, that is, down to the size of a lymphocyte. This holds 
both for the myelocytes in the circulating (leukaemic) blood and for 



70 



CLINICAL BLOOD EXAMINATION. 



those in the marrow. No distinction from other varieties of leuco- 
cyte can be based on size alone, unless we say their average size is 
greater than the average size of the leucocyte. Perhaps the follow- 
ing table may be of interest : 

Average diameter of 100 myelocytes =15.75 /v. 

" " " 100 polymorphonuclear neutropliiles =13.50 /i. 

" " " 100 "large " lymphocytes =13 

" " " 100 eosinophlles =12 ^. 

" " " 100 "small " lymphocytes =10 

" " " 100 red corpuscles (normal) ==7.5 /u.. 

EosmoPHiLic Myelocytes. 

Under the same conditions which favor the appearance of the 
ordinary (neutrophilic) myelocyte, we often find a small number of 
cells identical with them in all respects, except in possessing eosino- 
philic in place of neutrophilic granules. Such cells are found in 
abundance in the inarrow, and this fact together with the resem- 
blance to the ordinary myelocyte both in morphology and in the 
conditions of their occurrence, seems to me to justify the term 
eosino2?hiliG myelocyte. In them as in all myelocytes there is a 
wide variation between the staining affinities of different granules, 
some being much darker than others. 

So far I have described the type cell of each variety. As we 
should expect, atypical forms are numerous. Some of the com- 
moner ones are as follows : 

I. Degenerated Leucocytes. 

Frequently in leukaemia and occasionally in other conditions one 
sees leucocytes apparently moribund. That they are not always 
artifacts is shown by the fact that they are not found in normal 
blood treated by the same technique that reveals them in the blood 
and in hardened blood clot of leuksemic cases as well as by the fact 
that Botkin and others have produced similar appearances by keep- 
ing the leucocytes a few days in an aseptic state. 

The commonest forms of degenerated leucocytes are : 

1. A homogeneously stained mass looking like a washed out, 
structureless nucleus that has lost its protoplasm and become ragged 
at the edges (karyolysis). 

2. The same intensely stained. 



FINER STRUCTURE OF THE BLOOD. 



71 



3. Vacuolization of the nucleus or of the protoplasm. 

All these forms of degeneration aft'ect chiefly the lymphocytes 
and large mononuclear forms. In the granular leucocytes we see 
all stages of breaking up ; the granules are scattered about the field 
and the nucleus is pale, structureless, and deformed. 

II. Transitioxal Neutrophiles. 

Cells on the borderland between the "marrow cell" and the 
"polymorphonuclear leucocyte," the nucleus having some of the 
characters of each variety (see below, p. 110). 

III. Turck's "Stimulation Forms." 

These cells are also described by Engel as "mononuclear cells " 
and very recently by Weil as "non-granular myelocytes." 

Weil's description conveys the salient points in the appearance 
of this cell. It looks like a myelocyte whose granules have been 
fused into a smooth homogeneous band of color around the single 
spherical or ovoid nucleus. The protoplasm is always homogeneous 
and deeply stained; there is, however, a good deal of variation in 
the tint in different cells. In some it is purple, in others violet 
or brown. In leukaemia they are often counted as myelocytes or as 
large lymphocytes by unpractised observers. 

They appear in various diseases associated with stimulation of 
the hone marrow^ i.e., grave anaemia and all conditions associated 
with leucocytosis (see below, p. 110). 

Other rare varieties will be mentioned under leukaemia. 



PART III. 

GENERAL PATHOLOGY OF THE BLOOD. 



CHAPTER VI. 

UNEQUAL DISTRIBUTION OF BLOOD— POLYCYTHJEMIA— DILU- 
TION AND CONCENTRATION OF THE BLOOD. 

1. Unequal Distribution. 

How far is the single drop used for blood examination typical 
of tlie whole? 

It has been experimentally proved that specimens of the blood 
of the smaller venous and arterial twigs do not differ from each" 
other materially in corpuscular richness. Capillary blood is slightly 
richer in corpuscles than that either of veins or of arteries. But as 
capillary blood is everywhere of the same corpuscular richness, we 
may consider one capillary network or set of venules as typical as 
another, provided our technique is good, that is, provided lymph is 
not squeezed into the drop by strong pressure. It is indifferent, 
therefore so far as accuracy is concerned, whether the drop of 
blood be obtained from one or another part of the body. All 
standard estimates of the number of corpuscles per cubic millimetre 
of normal blood refer to capillary blood. 

2. Local or Peripheral Pohjcythmmia. 

So far we are speaking of normal conditions. It is a familiar 
fact, however, that the vessels of a given part of the body can be 
overcrowded with blood, e.g., by the use of an Esmarch bandage. 
A drop taken from such a part would certainly not be typical. 
Now as the same effect can be produced by a variety of diseases. 



GENERAL PATHOLOGY OF THE BLOOD. 



73 



under these conditions we must modify considerably any inferences 
made from examination of a single drop. 

Such conditions, entailing a false polycythsemia or apparent in- 
crease in the number of corpuscles are : 

Any disease involving either (a) general cyanosis or (b) cyanosis 
of the part from which the drop of blood is drawn. 

(a) Genei-dl cyanosis results from cardiac insufficiency (valvular 
or parietal disease of the heart itself, blocking of the lung circula- 
tion by emphysema or thrombosis), from insulficient aeration of 
the blood (pneumonia, congenital malformation of the heart), inter- 
ference with the heart's action by pressure of tumors, effusions 
(pericardial, pleural, peritoneal), or enlarged organs (liver, spleen), 
or from vasomotor disturbances. It is evident that some of 
these conditions {e.g., congenital heart disease) may not involve 
any peripheral stasis at all, and in the absence of this it is not 
easy to account for the increased number of corpuscles in the drop. 
Some observers have supposed that there is a real overproduction of 
blood cells under these conditions ; others suppose that the life of 
the individual corpuscle being lengthened, reproduction of cells at 
the normal rate soon leads to the "glut." There seems to be no 
reason to suppose that there is in these cases any unequal distribu- 
tion of cells in favor of the periphery, such as is obviously the con- 
dition in ordinary cyanosis with stasis. Whatever the explanation 
may be, there is no doubt of the fact that general cyanosis from any 
cause whatever produces an increase of cells in a drop such as we 
usually examine. 

The cases of cyanosis which I have classed under " vasomotor " 
(for want of a better explanation) , cases in which, in the absence of 
disease m any organ, the skin and mucous membranes are persis- 
tently and markedly bluish, are not very uncommon. I have seen 
three such, all in stout, elderly Avomen. In one the cells in a drop 
of blood from the ear, finger, or toe were more than double the nor-^ 
mal number (see below, page 75). 

(b) Local Cyanosis. — The pressure of a tumor, or any other 
hindrance to the circulation of any part, may give a similar increase 
m the number of corpuscles in a measured amount of blood from 
that part. In paralyzed patients the count may be higher on the 
paralyzed side. 

In markedly cyanotic patients the count of red cells may be 
notably above normal, and we must make allowances. Error is more 



74 



CLINICAL BLOOD EXAMINATION. 



likely to arise when we have cyanosis in a person whose blood is 
poor in red corpuscles. The combination of these two factors may 
give us a normal blood count and lead us to overlook the anaemia. 
Thus a person might have really a severe anaemia and yet the count 
of red cells be actually above the normal. This element of stasis 
should never be lost sight of. Many high counts reported in pneu- 
monia or hysteria are to be explained by abnormalities not of yro- 
duction or destruction but of distrihution of the blood cells. 

With these exceptions the drop of blood taken at the periphery 
is typical. We have next to consider some general conditions under 
which a person's whole blood may be inferred to be abnormal from 
the findings in a drop taken from the periphery. Consideration of 
special diseases will follow later. 

Temporary increase or diminution in the amount of fluid within 
the vessels can be brought about not only by a change in the me- 
chanical conditions of pressure and osmosis, but by any influence 
affecting the tone of the peripheral vessels. We have then : 

Tempovary Serous Pletliora or Dilntion of the Blood- 

{a) Erom transfusion of fluid in large amounts or its ingestion 
by mouth or rectum. 

ilj) From decreased blood pressure, as in acute failures of com- 
pensation in cardiac disease. 

(c) From vasomotor dilatation. 

As an example of this last Grawitz reduced the specific gravity 
of the blood from 1041 to 1038.7 within eight minutes by the in- 
halation of nitrite of amyl. This decrease of specific gravity can 
only mean an increased amount of watery constituents in the blood, 
as there was no evidence of any destruction of the heavier elements 
of the blood, and only water (and chlorides) pass through the ves- 
sel walls easily. In the above case the specific gravity was again at 
1041 within a few minutes. 

Polycythoimia. 

The red-faced persons popularly known as " full-blooded " show 
no abnormalities in their blood discoverable by any means of in- 
vestigation known to us. The condition is probably dependent on 
the presence of a rich capillary network near the surface of the 



GENERAL PATHOLOGY OF THE BLOOD. 



75 



skin, or a dilatation of individual venules and arterioles at the peri- 
phery. Such a person may be markedly anaemic without any con- 
siderable changes iii the color of the face. The fact that people of 
such complexion often end their lives with a ruptured cerebral 
artery is due presumably to the circumstance that " high living " 
produces in the same individual dilated peripheral capillaries and 
weakened arterial walls. 

Examples of what seems more likely to be a true polycythsemia 
are as follows : 

(a) In cases of severe anaemia which recover, the blood regen- 
eration may attain such vigor that the number of red cells shoots 
temporarily up ahove normal, even as high as 7,700,000. 

(l>) The same condition can be temporarily produced by trans- 
fusion of actual blood from one individual to another. It lasts but 
a few days as a rule. 

(c) Some cases occur without any known cause. In one such 
case which came to autopsy (death from cerebral hemorrhage) 
the internal organs were as deeply engorged as the periphery of 
the body. The three cases of the following table are apparently of 
this type. 

The polycythaemia of the new-born, of high altitudes, and of 
phosphoros poisoning ^Y\\\ be discussed later. 



Table I. — Polycythj^mia. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Haemo- 
globin. 


Remarks. 


29 




8,484,000 


15,000 


85 


February 5. Polynuclear, 84.6 ; lympho- 












cytes, 13.8 ; eosinophiles, 1.6. 








17,600 




February 8. Polynuclear, 90.4 ; lympho- 












cytes, 8 ; eosinophiles, 6 ; myelocytes, 1. 


66 




6,240,000 


10,000 


65 


First day. 






4,680,000 


5,600 


70 


Eighth day. 


53 




ll,a52,000 


8,300 


105 


December 6. 






9,260,000 




105 


December 7. After walking. 






10,060,000 




110 






10,400 a. c. 




December 11. 








11,700 p.c. 










10,230,000 


8,800 


110 


December 17. Polynuclear, 77.25 ; lympho- 










cytes, 18.75; eosinophiles, 2.75 : myelo- 












cytes, 1.25 ; microblasts, 2 ; normoblasts, 












2. Few mast cells. 



Concentration of the Blood. 

It is obvious that influences opposite to those producing tem- 
porary full-bloodedness will produce temporary lack of fluid within 
the vessels. So acute diarrhoea, purgation, deprivation of liquids 



76 



CLINICAL BLOOD EXAMINATION. 



(as in starvation), rapidly accumulated serous effusions, profuse 
vomiting or sweating (by skin and lungs) produce a temporary con- 
centration of the blood by draining out its diffusible elements (water 
chiefly) (see Table II.). All these influences are transitory. More 
permanent drains on the system, like chronic diarrhoea, diabetes 
insipidus or mellitus, or long-standing suppurations, show no evi- 
dence of lessening the volume of blood in the vessels. They drain 
albumin out of the serum and corpuscles and so decrease the weight 
of the blood (see below, page 83), but the blood volume is not 
changed. Indeed, any influence has to work very quickly in order 
to concentrate the blood, for in an astonishingly short time the other 
tissues repay the vessels their loss of fluid and the normal blood 
volume is restored. 

The same temporary effects can be produced by influences con- 
stricting the vessels (cold, pain, suprarenal extract), and a concen- 
tration of the blood results which lasts a few minutes or hours. ^ 

In all these interchanges of contents between the blood-vessels 
and the other tissues it is, as above said, the watery elements chiefly 
that change. The red cells are not affected by the give-and-take of 
the vessels and tissues, and although cold produces in the peri- 
pheral circulation an increase in the number of white cells greater 
than can be accounted for by simple concentration, the weight of 
evidence seems to be against any new production of cells and in 
favor of a change only in distribution, the white cells accumulating 
at the peripher5^ 

Now as the number of cells is not affected by these temporary 
variations in the volume of liquid within the vessels, it follows 
that the number to be coimted in a cubic millimetre, though typical 
of the whole blood at that time, is not to be reckoned from in the 
ordinary wayc For example, after a severe diarrhoea or in phthisis 
after a night-sweat the blood may be temporarily so concentrated 
that we flnd 6,000,000 or more red corpuscles per cubic millimetre. 
Under normal conditions of the blood mass we should infer from 

^ OHver has shown recently (Lancet. June 27th, 1896) that any influence 
causing rise of blood pressure will slightly concentrate the blood. Thus rais- 
ing the arm over the head and holding it there by muscular effort slightly 
concentrates the blood in that arm. Electrical stimulation or massage of the 
arm has the same effect. Lowering blood pressure, as when the arm is sup- 
ported passively over the head, dilutes the blood. This conlirms the results of 
Mitchell (Med. News, May, 1893) and of Cheron (Comptes Rend, de I'Acad. 
d. Sciences, 1896, No. vi.). 



GENERAL PATHOLOGY OF THE BLOOD. 



77 



such a count that the body contained one-sixth more red corpuscles 
than usual. Here obviously it means only (if anaemia is absent) 
that the blood mass is reduced one-sixth by concentration. It 
is only in such sudden reductions of blood volume that we can 
measure the amount lost by this method. Long-standing causes of 
drain on the plasma might at any time act as destroyers of red cor- 
puscles as wellj through the changes in the nutritive fluids in which 
they live. 

Further, it is only when we know the number of corpuscles just 
before the sudden drain on the plasma comes, that we can measure 
the amount of plasma lost by the amount of ajjparent increase in the 
red cells. Stasis and any other cause that heaps up corpuscles at 
the periphery must also be excluded before we can judge of the loss 
of plasma in this way. 

The conditions of an abnormal concentration of the blood are 
those already alluded to as temporarily sucking away its watery 
constituents, namely : 

{a) Watery diarrhoea, especially in cholera and other acute dis- 
eases accompanied by diarrhoea ; 

(h) Large and rapidly accumulating serous effusions (slow ac- 
cumulations would give time for the blood to take up water from 
the tissues and make up for its loss) ; 

{<:) Profuse sweats; 

(d) Persistent vomiting or starvation of liquids (see Table II.) ; 

(e) Increased blood pressure (exercise, massage, electricity). 
Blood alread}' lacking in red cells, if suddenly concentrated by 

such a loss of fluid, might deceive us into supposing it normal, be- 
cause the number of cells in a cubic millimetre might be normal. 
In the jjresence, therefore, of any such reason for concentration of the 
hloud. ice should aJu-aifs niodfy our ordinary methods of inference 
from the hlnnd count. For example, v. Limbeck records a case of 
hepatic cirrhosis with ascites, in which before tapping the ascites the 
count of red cells was 3,280,000 per cubic millimetre. AYithin 
twenty-four hours after tapping there were 5,160,000 cells per cubic 
millimetre, the re accumulation of the ascitic fluid going on so fast 
that the blood was unable to adjust itself and became overconcen- 
trated. A careless observation might have inferred a great gain in 
the corpuscular richness of the whole blood, when in fact not a cor- 
puscle had been gained and those present had probably grown poorer 
m albumin. 



78 CLINICAL BLOOD EXAMINATION. 



Table II.— Starvation. 



Case. 


Age. 


Red cells. 


White cells. 


Hiemo- 
•rlobin. 


Remarks. 


1 
2 


23 
2 


12,000.000 
8,780,000 


10,000 


V20 + 


Stowaway. Ten days Avithoiit food. 
Two weeks' starvation after caustic 
potash stricture of gullet. 







It remains to speak of two other conditions in which what aj)- 
jjears to be a true polj^cythaemia is fonnd: 

1. In persons living at high altitudes; 

2. In persons suffering from phosphorus or CO poisonmg. 



1. TJie Blood in Higli Altitudes. 

The potycythsemia of those living at high altitudes increases the 
higher ones goes. Koppe' gives the following table : 



Place. 


Height above 
sea level. 


Red cells. 


Author. 




O 


4,974.000 


Laache. 




148 metres 


5, 225, 000 


Schafer. 




314 " 


5, 822, 000 


Reinert. 




414 " 


5, 752, 000 


Stierlin. 




425 " 


5, 748, 000 


Koppe. 




700 " 


5,900,000 




1,800 " 


7,000,000 


Egger. 


The Cordilleras 


4,892 " 


8,000,000 


Viault. 



This extraordinary change takes place within two weeks of the 
time of taking up residence in a high place, and independent of 
any change in diet or manner of living. The sick and the well are 
equally affected and animals show similar changes. The haemoglo- 
bin is also considerably increased, although it lags somewhat behind 
the corpuscles. 

The corpuscles are often deformed and undersized during the 
earlier wrecks of the change ; but their volume, as determined b}' the 
hsematocrit, is not increased. These changes suggest that the im- 
mediate increase in the number of red cells is due to budding or di- 
vision of the cells already present in the circulation. 

Later the poikilocytes and microcyi;es vanish and the hsemoglo- 

' Munch, med. Woch.. 1890. Xo. 41. 



GENERAL PATHOLOGY OF THE BLOOD. 



79 



bin percentage rises so as to correspond with the increased count of 
red cells. 

On returning to low-land, the blood returns within a short time 
to its normal condition. 

Many explanations have been offered for this interesting phe- 
nomenon. If it were a true new production of corpuscles we should 
expect some signs of blood destruction (icterus, hsemoglobinuria) on 
returning to the sea level. But there are no such signs. On the 
other hand, if the polycythsemia were a simple result of concentra- 
tion due to the dryness of the high air, one would expect that the 
blood would quickly adapt itself, as in other (temporary) concen- 
trations, by taking up water from the tissues. But in fact it does 
not do so. The cause of the increase is still a mystery. 

2. Phosphorus and CO Poisoning. 

The polycythsemia of acute phosphorus poisoning may reach as 
high as 8,650,000. This may be partly explained by concentration 
due to the occurrence of vomiting, but in some cases the increase 
seems out of proportion to the amount of vomiting. 

With illuminating-gas poisoning there is usually no vomiting to 
speak of, and the cause of the marked mcrease in the red cells is 
unknown. Von Limbeck in two cases of CO poisoning showed re- 
spectively 6,630,000 and 5,700,000 red cells. Mlinzer and Palma' 
record 5,700,000. The white cells are also increased (see page 
363). 

^Zelt. f. Heilk., vol. xv., p. 1. 



CHAPTER VII. 
'anemia and hydremia. 



1. Anemia. 



Definition. — A deficiency in corjmscle substance, i.e., a deficiency 
in red. corpuscles, in haemoglobin, or in both,' with or without 
changes in the total volume of the blood. 

It is important to bear ui mmd that the color of the skin is not 
a safe guide in judging whether a person is anaemic. Thus out of 
100 cases shown to be anaemic by actual blood examination, To-vvn- 
send ^ found a good color in the cheeks of 4 and a fair color in 7 
others. Eighty-nine were pale. The color of the lips is but little 
better as a guide, as the following table from Townsend's article 
shows : 

Table of Colo?' in One Hundred Cases of Ancemia. 



Pale. 


Fair. 


Good. 


95 


5 


0 


89 


7 


4 


84 


15 


1.2 


76 


21 


2.4 


64 


25.5 


10.5 



Nails 

Cheeks 

Tongue 

Lips 

Conjunctivae. 



My own impression would be that the lips and conjunctivae were 
better guides than they are shown to be in this table. 

In examining the color of the nails, the fingers should be flexed, 
as full extension may partly cut off the circulation under the 
nails. 

^ This is a cHnical definition and makes uo attempt to go to the root of the 
matter. I have Httle doubt that chemical or other changes in the serum are 
the cause of the corpuscular changes, which only mirror the deeper disease. 
But these chemical changes are as yet so little understood that we have to 
judge of their presence chiefly by their effect on the corpuscles. 

Townsend : Boston Medical and Surgical Journal, May 28th, 1896. 



ANEMIA AND HYDREMIA. 



81 



A. K. Stone' and his assistants estimated the haemoglobin of 
189 female patients who looked anaemic, and found over 75 per cent 
of haemoglobin in 89, or nearly one-half of them. Tor a woman a 
haemoglobin percentage of 75 per cent or more means practically 
normal blood. - 

The most striking example of the fallacy of judging of anaemia 
by the color of the skin and mucous membranes is in the so-called 
^Hropical ancemia.^^ Practically all persons belongmg to white 
races who take up their residence in the tropics acquire after a time 
an extreme pallor of the skin and mucous membranes, and this ap- 
pearance has usually received the title of "tropical anaemia." It 
turns out, however, from the careful studies of several different in- 
vestigators, that the blood of such persons shows absolutely no 
anaemia or other variation from the normal.^ The appearance of 
the skin is probably due to the action of the extreme climate on the 
peripheral nerves and vessels. Tropical anaemia is a condition not 
of the blood, but of the skin and subcutaneous tissues. 

Every one's experience includes a few persons Avho are perfectly 
well despite an almost bloodless condition of the skin. 

On the other hand, anaemia may exist when there is a good 
color in the face. 

We are to judge of anaemia, then, solely by the blood examina- 
tion, and this judgment can be accurately made on the basis of the 
small fraction of a drop used for examination, ^jrovided always that 
our technique is good, and provided we make allowances for a con- 
siderable error whenever there is reason to suppose that any venous 
and capillary stasis is present, or that the blood is temporarily con- 
centrated or diluted. 

Distinction between Primary and Secondary Ancemia. 

In one sense all anaemia is secondary. It is due to some cause, 
a symptom in a chain of events. But in some cases we know the 
cause and in some we do not. 

(a ) PriDutry ancemia is that in ivhichthe causal factors are either 
entirely imknoivn or are apparently insufficient to produce so severe a 
disease. This division, like most of our statements about the blood, 

^Boston Medical and Surgical Journal, August 23d, 1894. 
^ When the haemoglobin is high the number of corpuscles is never consid- 
erably diminished. 

^ So far as present methods of examination go. 
6 



82 



CLINICAL BLOOD EXAMINATION. 



is a rough-and-ready one, held to provisionally until a better classi- 
fication is discovered. It has a certain utility if not used with any 
less simple meaning than that given above. 

There is no good evidence that there are any primary dis- 
eases of the blood-making functions. A case of secondary anae- 
mia is one in which we have an obvious cause such as hemorrhage 
or malaria for the loss of corpuscle substance. Remove the cause 
and the anaemia ceases. Sometimes, however, after removal of the 
cause, e.g., after cure of a case of syphilis, the anaemia set agoing 
by the syphilis persists. On the other hand, there are few patients 
with "primary" anaemia who cannot recall some event in their past 
lives sufficient to account for a certain (jrade of anannia (e.y., a 
nervous shock, a hemorrhage, an attack of tertian malaria) . Yet 
if the anaemia that occurs after so slight a cause is of the pernicious 
or fatal type, we may fairly call it "7;>?'im«ry." By this we mean 
that though the "cause" assigned might produce some anaemia, it 
was not sufficient to produce this fatal anaemia and has presumably 
little or no connection with it. "Primary" means not the absence 
of any cause of anaemia in the history, but the absence of any suffi- 
cient cause so far as is known. 

An attack of tertian malaria or a history of bleeding piles does 
not cause fatal anaemia in 999 out of 1,000 people who have such a 
history. In the 1,000th it is a case ot jjost hoc smd not 2yropter hoc. 
Given the unknown cause that does lead to " primary " anaemia, and 
it might be that a pregnancy, a nervous shock, or the presence of 
intestinal parasites would act as the straw that breaks the camel's 
back; but the imjwrtant causal factor is the unknoicn factor. Evi- 
dence is accumulating in support of Hunter's view that j^ernicious 
anaeania is due to excessive blood destruction produced by toxic sub- 
stances absorbed from the gastro-intestinal tract. Chlorosis is now 
generally believed to be a disease representing defective blood- 
formation. But we are still in the realm of theory in these matters. 

It is true that in the majority of cases we can tell from the blood 
examination alone whether a case is without known cause (= " pri- 
mary") or symptomatic (= "secondary"). But there appear to 
be enough exceptions to this rule to make us cautious about stating 
it as a law. 



Anemia = ^ 



{ Primary = 



j Chlorosis. 

{ Pernicious anaemia. 



f To be discussed under Special 
s Pathology of the Blood, 
[ Chapter VII. 



Secondary. 



ANEMIA AND HYDREMIA. 



83 



Secondary Ancemia. 

I. First Stage. — I defined ansemia above as a dlndniition in cor- 
puscle substance. In tha milder types of this condition the number 
of red corpuscles is not diminished at all, but the individual cell is 
small, pale, and of light weight, through loss of nitrogenous mat- 
ter. This is appreciated : 

(«) As a lack of coloring matter ; 

{b) As a lowering of the specific gravity. 

In the mildest grades of secondary anaemia there are no further 
changes. Such cases are those due to errors in hygiene — bad air, 
poor food, lack of light or exercise — to small hemorrhages, and to 
the earlier stages of the diseases next to be mentioned. 

The lack of coloring matter is usually not present m every cell, 
as is seen in the stained specimens. Some are very pale at the cen- 
tre, while others are well stained. 

II. Second Stage. — Usually the next changes to appear are, like 
those already mentioned, <iucditative, ihQ number of red cells still 
remaining normal or approximately so. 

The individual cell as seen in fresh preparations is more or less 
deformed and varies from its normal diameter, dwarfed forms 
usually being commoner than the giant forms. These variations 
in size and shape are sometimes termed i^oikilocytosis" and the 
dwarf and giant forms are called respectively microcytes and ma- 
crocytes. 

Maragliano' has included the above changes, together with others 
about to be described, under the heading of 

Necrobiosis in the red corpuscles, attributing them to a patholog- 
ical condition of the serum. 

The changes united under this heading may be divided for con- 
venience' sake into 

{a) Endogiobular changes. 

(b) Poikilocytosis and crenation. 

(c) Changes in staining properties. 

{d ) Changes involving motility in the corpuscle as a whole, or 
in parts of it. 

(e) Decrease in the average diameter of corpuscles with loss of 
the power to form rouleaux. 

All these changes may be watched in normal blood outside the 
iXI. Cong. f. Inn. Med., Leipzig, 1892. 



84 



CLINICAL BLOOD EXAMINATION. 



vessels, as necrosis gTadually comes on from contact with the air. 
Under pathological conditions the same changes may occur outside 
the hodij, but more quickly than usual (as other diseased tissues 
decompose more quickly after death than those of a sound man 
suddenly killed), or inside the hodij. 

(a) Endoglohular Changes (see Fig. 26, a). — These consist in 
the appearance of clear hyalme spaces of various shapes within the 



and presumably they were present before it left the vessels. 

[b) Crenation and Foihiloeytosis (Fig. 26, — What we know 
as crenation in the corpuscles is probably the same sort of proc- 
ess which, occurring within the vessels, we call poikilocytosis. A 
lump rises at one or more points in the corpuscle, becomes more 
pointed, and gradually the whole cell acquires amoeboid motions, 
assuming in succession the various shapes with which we are famil- 
iar in poikilocytes. Haj^em has mmutely described four types of 
motion in the red cells of anaemic blood, 

1. General amoeboid motion of the whole cell. 

2. Vermicular motion of flagella-like prolongations. 

3. Oscillating motions, especially in small light cells. 

4. Pseudo-parasitic motion. 

{(') The pointed projections may break off and move about ac- 
tively in the plasma. These motions, as well as the preceding 
amoeboid movement of the whole corpuscle, are to be explained as 
irregular contractions of the necrobiotic protoplasm, similar in a 
general way to the actions of a hen after its head is cut olf. These 





:iye Changes in Red Cells. 



corpuscle, round, triangular, 
rod - shaped, etc. In the 
fresh specimen they change 
their shape rapidly and 
continnally; in dried and 
stained specimens they ap- 
pear as sharph' outlined 
light spaces in the corpus- 
cle. In normal blood these 
changes occur after thirty 
to seventy mmntes outside 
the vessels. In some path- 
ological conditions' speci- 
mens show them the in- 
stant the blood is collected, 



ANEMIA AND HYDREMIA. 



85 



motions are not to be confounded with the finer Brownian or "mo- 
lecular " movement to be seen in any healthy cell. The small bits 
broken off (Fig. 26, e) are doubtless the dwarf cells seen in dried 
and stained preparations. Curiously enough, these fragments tend 
again to assume the biconcavity characteristic of normal cells, as a 
drop of fat breaks into smaller but similar drops. 

(d) Oval sliaioe. — A great many cases of pernicious anaemia and 




Fig. 27.— Elonprated or Oval Corpuscles in a Case of Pernicious Anaemia. 



some other diseases (see Epidemic Dropsy, page 256) show a 
marked tendency to oval shapes in corpuscles not otherwise consid- 
erably deformed. Even in normal blood I think there are a small 
number of oval forms, and in anaemia this number may be greatly 
increased till, as in Fig. 27, we get all the cells elongated. The 
same appearance can be produced by roughness in spreading the 
blood, but in such case the deformed corpuscles all point one 
way. 

(e) Changes in Staining Fvopert'ies. — Normal red corpuscles have 
affinity chiefly for acid stains. The same degenerative changes 
that lead to the alterations in shape and size above described alter 
the staining properties of the cell as well, so that it takes up two or 
three colors (according to the number present in the stain), either 



86 



CLINICAL BLOOD EXAMINATION. 



as a diffuse mixture or irregularly, some parts of the cell taking 
color differently from others. In lead poisoning minute bits of the 
red cells become basophilic, so that the cell presents, with appro- 
priate staining, a stippled look. The same change occurs in per- 
nicious anaemia and occasionally in other varieties of anaemia. This 
has been termed a polychromatopJiillc^^ or degenerative change. 
Some observers have supposed it to be rather of the nature of re- 
generation, believing that the cells take color in this unorthodox 
way because they are half- developed. 

(/) In many secondary anaemias, especially in those associated 
with inflammations, the average diameter of the cells is lessened, 
and the rouleaux are not formed. ^ 

{g) Cells may lose their haemoglobin altogether, leaving only 
the shell of the corpuscle behind (see Fig. 26, d). 

Now all these necrobiotic changes are characteristic of the se- 
verer grades of secondary anaemia such as occur in cancerous 
cachexia, phthisis, nephritis, etc. 

In pernicious anaemia they are, as a rule, much more marked 
than in any other disease. Maragliano considers these degenerative 
changes to be due to toxic plasma. A lessened resistance to the 
ordinary plasma-environment on the part of the red cells would also 
explain them, and in such affections as paroxysmal haemoglobinuria 
it seems the most probable cause. In syphilis the abnormal sensi- 
tiveness of the red cells to the influence of mercury seems another 
instance in which the red cells are immature, decrepit, or weak. In 
syphilitic children, for instance, mercury easily gives anaemia, while 
in healthy children it does not. This will be discussed more fully 
under syphilis. 

The necrobiotic phenomena above described have been observed 
by Maragliano in carcinoma, lead poisoning, leukaemia, pernicious 
anaemia, purpura, cirrhotic liver, nephritis, pneumonia, malaria, 
typhoid, erysipelas, and tuberculosis. Celli and Guarnieri (Fort- 
schritte der Medicin, 1889, No. 14) found them in measles and scar- 
let fever. Weintraub {Virchow^s Archiv, vol. cxxxi.) noted them 
in epilepsy, pyaemia, and catarrhal jaundice. 

A decreased resistance to pressure, to electric currents and other 
influences has also been noted by v. Limbeck in some cases. 

Such weakening of the red cells experimentally produced in ani- 

' But in the severest forms of anaemia the diameters are apt to be increased 
(see below, Pernicious Antemia). 



ANEMIA AND HYDREMIA. 



87 



mals by poisons has been found (Mya and Sanarelli, Arch. ital. di 
Biolog., xvii., 1892) to increase the susceptibility to infectious 
diseases. 

III. Third Stage. — Here the mnnher as well as the quality of 
the red cells begins to suffer. So far I have mentioned only the 
qualitative changes in secondary ansemia and have purposely made 
these changes more prominent than the actual diminution in the 
count of red cells, because it is only comparatively rarely and in 
very marked cases that the diminution in red corpuscles is con- 
siderable. The blood characteristic of most cases of secondary 
anaemia is one in which the number of red cells is approximately 
normal. 

The important exceptions to this rule are: 1. The anaemias of 
infancy and early childhood. 2. Large hemorrhages (soon after 
their occurrence). 3. Malaria. 4. Acute septicaemia. 

The direct and rapid destruction of the corpuscles by the mala- 
rial organism or hemorrhage account for this. Of sepsis and the 
anaemias of infancy I shall speak later. 

lY. Fourth Stage. — The blood of secondary anaemia shows of ten 
evidence not only of degeneration and destruction of the cells but 
also of regenerative changes, namely : 

Nucleated Red Cells. 

These are usually divided into three groups 

(a) Normoblasts. 

(b) Megaloblasts. 

(c) Microblasts. 

Normohlasts. 

(a) The first are normally present in moderate number in the 
bone marrow of healthy persons, and in great numbers in the mar- 
row after hemorrhage. They are generally considered to be a 
younger stage m the life of the corpuscle than the non-nucleated 
forms seen in the circulating blood. Hence the appearance in the 
peripheral circulation of this form of nucleated cell is considered to 
mean that, in the comparatively plentiful reproduction of red cells 
called forth in the marrow by the anaemia, a certain number of red 
cells leave the nursery (the marrow) before they are grown up and 



88 



CLINICAL BLOOD EXAMINATION. 



circulate for a time in tlieir immature state. A normoblast, then, 
represents an immature red corpuscle (see Plate IV.). 

In size and color it is like an ordinary red cell except that we 
find, usually somewhat to one side of it, a round nucleus about one- 
half the diameter of the whole cell. With Ehrlich's tricolor mix- 
ture, this nucleus stains very deep blue, nearly black, and is sharply 
outlined against the pale yellow of the cell body around it. 

The cell often looks as if it were pushing its nucleus out, i.e., 
in many instances we see the nucleus projecting over the edge of 
the corpuscle, or half out of it, and occasionally we find it lying 
beside the corpuscle from which it has just emerged; but this ap- 
pearance is probably an artifact and not, as Ehrlich thought, the 
regular way of disposing of the normoblast nucleus. 

Very frequently the nucleus has toward the centre a light spot, 
sometimes so brilliant that it looks like the reflection of light from 
the surface of a drop of ink or any dark liquid, what artists call 
the "high light." Occasionally there are several of these light 
spots in a nucleus, or it may be all light blue-gray except a dark 
blue rim. This is the commonest type of normoblast. But now 
and then we meet with one when the nucleus is more or less sepa- 
rated into two or more pieces. These pieces are usually connected 
by pale-staining "bridges," perhaps radiating from a centre so that 
the nucleus is " rosette- shaped," or it may take any one of a large 
number of different shapes. The parts of the nucleus which are 
nearest the periphery of the cell usually stain more deeply than the 
"bridges" which join them. 

Sometimes the nucleus breaks apart completely and we find two 
or more separate unconnected nuclei within the single cell.^ Or 
one of the pieces may be outside the cell and the others inside. 

Rarest of all is the appearance of true mitosis in the nucleus of 
a normoblast. 

Megalohlasts. 

(h) The typical megaloblast as usually described is so unlike 
the normoblast that we should not naturally think of them as near 
relations. 

It does not occur anywhere in the healthy adult body, not even 
in the bone marrow. In the early foetal marrow and in the marrow 

' Apparently the nucleus is absorbed or degenerates (see Israel and Pap- 
penheim: Vircliow's Archiv, vol. cxliil.). 



ANEMIA AND HYDREMIA. 



89 



and circulating blood of grave forms of anaemia it is to be found, 
usually in company with a certain number of normoblasts. 

Ehrlich described megaloblasts as the sign or product of a differ- 
ent type of blood formation, namely, the foetal type, and considered 
those anaemias in which it occurs as tending to a return of the blood 
to the foetal state. [This has been recently confirmed by the re- 
searches of Pappenheim, though Ehrlich's detailed theory of two 
methods of blood formation is now generally discredited. All nu- 
cleated red cells lose their nuclei by " absorption " ; none by extru- 
sion.] Ehrlich regarded the presence of megaloblasts as a bad 
prognostic sign, and believed that a pernicious or fatal anaemia was 
characterized by an excess of these cells over the normoblasts. He 
recognized that they might be found in various milder forms of anae- 
mia ; but here the prevailing type is the normoblast, and regeneration 
may be more active than degeneration. In his general conception of 
the prognostic import of megaloblasts Ehrlich has been supported by 
the weight of later clinical observation, although it has been shown 
that the anaemia due to intestinal parasites can be cured, despite the 
presence of the megaloblasts as the prevailing type of nucleated red 
cells. So far as I know this is the only exception to Ehrlich's 
rule. 

The typical megalohlast is an abnormally large cell (11 to 20 jx in 
diameter, frequently showing marks of degeneration (polychromato- 
philia) in its protoplasm, which is therefore brownish or purplish 
with the Ehrlich-Biondi stain. Its nucleus is very large, filling 
most of the cell, and contrasts with the normoblast nucleus not only 
by its greater size but by the pale, even stain which it takes up. 
The commonest color of the nucleus with the Ehrlich-Biondi stain 
is pale green or robin' s-egg color. It is not stained evenly but 
dotted over with purplish granules arranged in a fine mesh like the 
knots in a fish-net (see Plate IV.). 

Outside the nucleus there is usually a retraction band of clear 
white, apparently an empty space, separating the nucleus from the 
encircling protoplasm. The protoplasm close round this colorless 
ring is usually stained more deeply than the rest of the cell. 
Cracks and " flaws " are sometimes to be seen in the protoplasm, 
giving evidence, as its purplish stain does, of the necrobiotic changes 
described by Maragliano. 

The outline of the whole may be quite circular : oftener it is oval 
or somewhat irregular, but rarely much deformed. 



90 



CLINICAL BLOOD EXAMINATION. 



Mlcrohlasts. 

(e) Microblasts, which are rarer than either of the varieties just 
described, consist of a nucleus like that of a normoblast or smaller, 
and contained in a cell body smaller than the normal red corpuscle. 
In the writer's experience the cell body is usually reduced to a few 
shreds of discolored protoplasm hanging about the nucleus (see 
Plate IV.). Their clinical significance is generally supposed to be 
that of megaloblasts. 

^''Atypical Fovms.''^ 

Often we find in a given specimen of blood only typical nor- 
moblasts, microblasts, or megaloblasts, and accordingly can easily 
reckon up the number of each kind and see which type of blood 
formation predominates. But sometimes there are cells present, 
about the classification of which we cannot come to a decision, and 
I have occasionally seen a specimen of blood containing a large 
number of nucleated red cells no one of iclikli could strictly be 
classed either as a "normoblast," a "megaloblast," or a "micro- 
blast," as these are defined above. 

The researches of Pappenheim have thrown much light on this 
difficulty. While insisting with Ehrlich that the megalo blast and 
the normoblast represent respectively the early foetal and the post- 
uterine types of blood formation, and that there are no real "trans- 
itions " from the one to the other, he yet recognizes that the two 
varieties are not ahsolutely to be differentiated by any of the ordi- 
narily accepted criteria such as size, color of nucleus, etc. Most 
"megaloblasts," he admits, are larger than most normoblasts, but 
there are occasional giant normoblasts and dwarf megaloblasts 
which by size alone are indistinguishable. The large, pale, deli- 
cately netted nucleus of the "megaloblasts" is simply a young nu- 
cleus. All young nuclei are relatively large and pale, while the 
small dark nucleus of the normoblast is simply an old or degener- 
ating nucleus. The real criteria of the two varieties, according to 
Pappenheim, is not the size or color of nucleus nor of the whole 
cell, but the structure of the nuclear network. This is a point diffi- 
cult to make out by ordinary staining methods and not easily appre- 
ciated. Luckily for us, most "megaloblasts" are larger than most 
" normoblasts " ; and further, most of them as seen in the blood are 
young (i.e., have large pale nuclei with delicate chromatin network), 



PLATE IV. 



(1) m,'in,m, m — Young megaloblasts. 

(2) D,D,D,D ; the upper ticosive probably o^rZ with degenerating 
nuclei, and the lower two old megaloblasts with nuclei in a similar condition. 

(3) 0,0,0,0, etc. — The two cells in the lower right-hand corner are probably 
old megaloblasts whose nuclei are nearly absorbed. The three cells immediately 
to the left of these are probably young normoblasts — the lowest one being the 
youngest. The other four cells marked ^''0,0,0,0'''' (those to the extreme left) 
are probably middle-aged megaloblasts. The two labelled " Normoblasts " are 
really old normoblasts. The appearance of extrusion of the nucleus on one of 
them is probably an artifact. The large cell on the extreme upper right-hand 
corner is probably a megaloblast with a " pyknotic " or (Edematous (degener- 
ating) nucleus. 

(4) In the young or "typical " megaloblasts {m,m,m,m) note the white line 
around the nucleus, the variations in its tint, and, in two of them, the discol- 
orations of the protoplasm (polychromatophilia), especially near the nucleus. 
The lower of the two cells in karyokinesis shows the best. 

(0) In the microblast note the ragged edge of the protoplasm. 

(6) In the lower portion of the plate {""cells deformed in size or sliape'''') an 
actual field from a case of pernicious anaemia was copied. Macrocijtes (or large 
cells), microcytes (or small cells), and misshapen cells or poikilocytes are shown. 

(7) The polychromatophilic celW'' in the lower right-hand corner were 
stained with the same mixture as those to the left of them, but have taken up 
other colors besides the orange G, which alone is taken up by normal red cells. 



Examination of the Blood. 

PLATE IV. 



Normal red cells 



1^ 



1^^- 



Normoblasts 



4#l 

Microblast 




it' 



Cells in karyo- 
" kinesis 



Varreties of Nucleated Red Cells. 

m, m. m. m. = Typical megaloblasts. D. D. D, D. = Cells with dividing nuclei. 
0. 0. 0, 0. o. 0. o. = Other (unnamed) varieties of nucleated red corpuscles. 



Scale of [J. 




Polychromatophilis cells 



Cells deformed in size or shape. 



R, C. Cabot fee. 



Liith. Airst. t. E. A. Funka, Leipzig. 



ANJSMIA AND HYDREMIA. 



91 



while most "normoblasts" are old, as shown by their small, dark, 
coarse-skeined nucleus, so that in the majority of cases Ehrlich's 
criteria for the two varieties are sufficiently correct for diagnostic 
purposes. Pappenheim of course wishes to abandon the terms 
" megaloblast " and " normoblast " altogether, but since size still 
remains the most easily recognized criterion of " megaloblasts " and 
"normoblasts" I shall continue to use the terms. On the chances, 
then, any nitcleated red cell over 10 [j. diameter sliould he classed as a 
megalohlast tvhatever the appearance of its nucleus, and any nucleated 
red cell under 10 ii. diameter is probably a normoblast w\i2iX,QYQx the ap- 
pearance of its nucleus. Microhlasts simply represent degenerating 
forms (usually normoblasts) whose protoplasm is falling away. 
The clinical significance of the two varieties is just such as Ehrlich 
supposed. [These points will be made clearer by reference to Plate 
IV. and the remarks intended to explain it.] 

In most cases of severe secondary ansemia we find a few normo- 
blasts. In very severe forms, whatever the cause, we may or may 
not find an occasional megaloblast. But these are much rarer than 
the normoblasts, even in the severest types of secondary angemia. 
The only exceptions to this rule are the anaemias due to intestinal 
parasites, in which, though secondary and curable, the megaloblasts 
in some cases predominate over the normoblasts. 

Summing up the changes characteristic of secondary anaemia, 
which includes almost all the important pathological appearances 
occurring in red cells, we have : 

i (a) Lack of haemoglobin. ^ 

I. (b) Lowered s p e c i fi c >■ Characteristic of mild cases, 
f gravity. ) 

II. The above and necrobiotic ) Characteristic of moderate 

changes of Maragliano. ) cases, 
f (a) Lack of red cells. "j 

III. J (b) Presence of normo- [Characteristic of severe 
1 blasts and the above f cases. 

[ (I. and II.). J 

IV. Megaloblasts and the above Characteristic of very se- 

(I., 11. , and III.). vere cases. 

The changes in the white cells will be discussed in the next 
chapter. 

Among the commonest causes of secondary anaemia are : I. In- 
fective and febrile diseases, acute or chronic. II. Malignant dis- 



92 



CLINICAL BLOOD EXAMINATION. 



ease. III. Chronic suppurations, nephritis, chronic dysentery, 
cirrhosis of the liver. IV. Bad hygiene, pregnancy, and lactation. 
V. Intestinal parasites. VI. Poisons (lead, arsenic, etc.). 

To discuss the way in which each of these influences acts in pro- 
ducing anaemia is tempting, but falls outside the plan of this book. 

The following are good examples of the condition of the blood: 



Secondary Anemia. 



No. 


Age. 


Red cells. 


White 
cells. 


Hgemo- 
globin. 


Remarks. 


1 


23 


1,656,000 


2,300 


18 


Post malarial. 






2,048,000 


2,600 


24 


Seven days' treatment. 






1,808,000 


3,200 


30 


Fourteen days' treatment. 






1,568,000 


1,300 


58 


Twenty-four days' treatment. 






4,248,000 


2,300 


60 


Thirty-four days' treatment. 




22 


1,540,000 


2,200 




Malaria and dysentery. 




23 


1,984,000 


6,700 




4 


21 


1,352,000 


3,300 




.1 


5 


24 


1,248,000 


6.000 




i(. I. 


6 


23 


1,931,000 


8,600 


35 


^Estivo-autumnal malaria. 

Polvnuclears, 73 ; lymphocytes, ,24 ; eosinophiles, 3 ; 
megaloblasts = 1 ; normoblasts, 4. 


ij- 


35 


3,070,000 


2,100 


35 


Tertian malaria. Boston. 


8 


29 


1^228^000 


25^,100 


9 


Tubal pregnancy, hemorrhage. Polynuclears, 92 5 
lymphocytes, 7 ; eosinophiles, 1 ; normoblasts — 6 ; 






















megalobiasts = 2. 


9 


50 


1,960,000 


13,400 


22 


Fibroid bleeding. Polynuclears, 85; lymphocytes, 14; 
eosinophiles, 1. 


10 


64 


1,824,000 


4,800 


25 


Htematuria. 


11 


25 


1,448,000 


3,600 


10 


Portal thrombosis, profuse hEematemesis. Polvnuclears, 
79 ; lymphocytes, 19 ; eosinophiles, 2 ; normoblasts = 
3 ; megalobiasts = 1. 






906,000 
3,200,000 




0 


Ten days later. Death next day. Autopsy. 
Hepatic cirrhosis. Ha?moptysis yesterday. 




QQ 




0.5 


13 


46 


2,992,000 


lo,olnJ 


QD 

4y) 


Metrorrhagia. 


14 


31 


2,500,000 


( ,OUU 


oU 


Chronic diffuse nephritis. 


15 


40 


2,040,000 


9,600 


10 


Chronic dysentery. Polvnuclears 66.3* myelocvtes 1.4' 
normoblasts = 8 ; megalobiasts = 5.' (Four hundred 
cells counted.) 


16 


53 


4,030,000 


12,700 


23 


nnplp?ir<5 S*^ • IvinriViOPvfp^ m* PHQinnnhllp* (i • irip- 

firaloblasts — 4 * normoblasts — 22. (Four hundred 
cells counted.) 


17 


33 


2,999,000 
3,584,000 


9,200 


3.5 


Chronic arthritis with ankylosis. 


18 


39 


12,000 


45 


Alcoholic neuritis. 


19 


30 


3,496,000 


11,000 


25 


Chronic gastric catarrh. 


20 


42 


3,020,0t» 


11,600 


50 


Tertiary syphilis. 


21 


25 


3,712,000 


10,200 


40 


Ovarian cyst. 


22 


11 


4,240.000 


11,600 


45 


Fi'iedreich's ataxia. 


23 


9 


4,270,0tH) 


9,200 


35 


Cervical Pott's. 


24 


58 


2,744,000 


4,000 


60 


Autopsy. No cause found. 


25 


59 


2,444,000 


4,700 


38 


Polynuclear, 73 ; lymphocytes, 25 ; eosinophiles, 2 ; nor- 












moblasts = 2 ; megalobiasts = 0. 
Polynuclears, 71 ; lymphocytes, 27.8 ; eosinophiles, 1 ; 
myelocytes, 2 ; normoblasts = 7 ; megalobiasts = 1. 
Autopsy, fibroma of jejunum (ulcerative colitis). 


26 


43 


1,468,000 


8,700 


12 




53 


1,472,0)0 


12,400 


20 


Duodenal ulcer. Polynuclears, 75 ; lymphocytes. 23.6 ; 
eosinophiles, 1.2 ; myelocytes, 2 ; normoblasts = 1. 






l,876,OK) 
2,148,000 
2,440,00) 
3,196,000 
2,774,000 




19 


Seventh day. 
Fourteenth day. 
Twenty-first day, 
Twentv-eiarhth day. 
Thirty-fifth day. 








17 








21 








23 






6,600 


28 








23 


Forty-third day. Polynuclears, 72.8 ; lymphocytes, 25 ; 
eosinophiles, 2 ; mast cells, 2 ; normoblasts = 1. 






2,820,000 




30 


Fiftieth day. 






3,440,000 




43 


Fifty-seventh day. 






3,832,000 




46 


Sixty-fourth day'. 






3,885,000 




48 


One hundred and second day. 



ANEMIA AND HYDR.EMIA. 



93 



2. Hydk.emia. 

(a) Seen from the opposite point of vie^v almost all cases of 
anaemia are liydrsemic. That is, if the total volume of blood is to 
remain approximately constant (as it appears to do), any loss of 
solids (corpuscle substance) mast be made up by water taken in 
from the tissues. Hence any anaemic person's blood is thin, wa- 
tery, or hydraemic. Women's blood is somewhat more hydraemic 
than men's, because less rich in cells. Ordinary chlorosis and 
secondary anaemia show no more water than normal in the serum, 
but the cells are probably somewhat water-logged. * 

(b) In many conditions of dropsy,' whether from heart or kid- 
ney, we may have more water than normal, both in the plasma and 
in the corpuscles themselves, which are capable of taking up con- 
siderably more than their normal amount of water. 

(c) Any temporary dilution of the blood under the conditions 
mentioned above (ingestion of liquid, lowered blood pressure, etc.), 
is from one point of view a hydraemic condition. 

Xo special clinical significance attaches to it other than that of 
anaemia, whose correlative it is. 

(d) The investigations of Haldane and Smith seem to show that 
the total volume of plasma is greatly increased in certain types of 
anaemia, although its sj^ecific gravity remains normal. This is one 
type of liydraemia (see page 6). 



CHAPTER A'lII. 



LEUCOCYTOSIS — LYMPHOCYTOSIS — EOSINOPHILIA — 
MYELOCYTES. 

Much confusion lias been caused in the past by the failure to see 
in leuksemic blood anything more than an extreme and permanent 
form of leucocytosis, while leucocytosis was thought of as a mild 
and temporary leukaemia. 

We know now that they are quite different phenomena, differ- 
ing not in the number, but in the kind of cells present in the in- 
creased numbers. 

Definition. 

There are many difficulties in defining leucocytosis. To my 
mind the term is best used to mean: Ati inrrease in tlte number of 
leucocytes in the peripheral blood over the number normal in the in- 
dividual case, this increase never involving a diminution in the pjoly- 
morphonuclcr rariffirs. hut (jeneralhj a marhed absolute and relative 
gain over tlte )iuird>er prerioushj present. 

((c) I say in the peripheral blood " because most observers now 
hold that leucocytosis is not always a real increase in the total num- 
ber of leucoc}-tes in the body, but is often the result of chemotaxis 
or thermotaxis, the cells being di^awn or attracted to the periphery 
and out of the internal organs. At any rate, in the blood drop 
which we draw (whether also in the internal organs or not), the 
leucocytes are present in increased numbers per cubic millimetre. 
The studies of Muir, Ehrlich, and others have made it clear that 
there are two types of leucocytosis. (1) The first includes only 
leucocytoses of sudden appearance and short duration such as those 
produced by cold baths. Here there is no time for the production 
of new cells and the increase of white corpuscles in the peripheral 
blood corresponds in all probability to a decrease in the number 
ordinarily hoarded in the pulmonary capillaries and elsewhere, the 
total number of leucocytes in the body remainmg approximately the 



LEUCOCYTOSIS. 



95 



same. (2) When leiicocytosis lasts for months, as is often the case 
in long-standing suppurations and malignant neoplasms, there is no 
doubt that leucocytes are formed and turned into the circulation 
more rapidly than under normal conditions. The total number of 
leucocytes in the body is then greatly increased. In such cases the 
marrow is found to be hyperplastic whether the leucocytosis is due 
to bacterial toxins (Eibbert) or to long-continued experimental in- 
jections of albumoses (Taylor). Chronic leucocytosis, then, is a 
function of the marrow. 

(b) In persons not usually to be considered sick, but simply 
somewhat wizened or ill-nourished, the normal count of white cells 
may be as low as three thousand per cubic millimetre. For such 
an individual ten thousand cells per cubic millimetre would be a 
decidedly pathological condition. On the other hand, there are 
persons, usually those of notable vigor and good nutrition, whose 
white cells rarely fall below ten thousand. 

Obviously we must take account of these differences both in our 
definition and in our practice if we are to reason correctly from the 
data of blood examination. 

(c) Further we must lay stress upon the varieties of leucocytes 
whose increase constitutes leucocytosis in distinction from either 
variety of leukaemia (myeloid, or lymphatic). 

For instance, given a count of eighty thousand leucocytes per 
cubic millimetre, we cannot tell without knowing the varieties of 
cells present whether the case is a genuine leukaemia or merely a 
leucocytosis symptomatic of pneumonia, suppuration, malignant 
disease, or other conditions. 

(d) Thus defined leucocytosis is of two kinds. 1. That in 
which the relative proportions of the different varieties to each 
other is unchanged. 2. That in which the increase is made up 
solely or largely by a gain in the polymorphonuclear leucocytes. 

The latter includes nearly all long-standing and pathological 
leucocytoses, the former being confined chiefly to the transient 
physiological leucocytoses next to be described. 

(e) Lastly, in order to be sure that the polymorphonuclear cells 
are not decreased, we must know approximately what the normal 
percentage for that individual is. The normal percentage of these 
cells in infancy is from twenty-eight to forty per cent. In adults 
it is much higher, but varies like the total count, according to con- 
ditions of nutrition, etc. Thus the normal for adults is usually set 



96 



CLINICAL BLOOD EXAMINATION. 



at from sixty to seventy per cent, and if we include the obviously 
ill-nourished, but not actually sick, and also those in blooming 
health, we shall have to widen our normal limits considerably. 
From fifty to seventy-five per cent are within normal limits accord- 
ing to the above conception. But obviously we can make no 
absolute judgment by a standard so vague. It is much better, I 
think, to consider each individual as his own standard within these 
limits, his count of polymorphonuclear cells being a fair measure of 
the soundness and vigor of his metabolism. Thus, in an obviously 
debilitated individual, we should consider seventy-two per cent 
of these cells very high, while in a vigorous athlete it might not 
be so. 

It is the endeavor to include all these limiting conditions that 
has made my definition so long and involved. It gives us, if it 
turns out to be true, some better way of classing individuals than 
as " sick " or " well " as regards their blood state. We find out how 
well or how sick their blood is (to a certain extent) , {a ) by the total 
number of leucocytes present, and {h) by the proportion of poly- 
morphonuclear neutrophiles in a given one thousand of these leuco- 
cytes. These data tell us approximately how normal or hoiv abnor- 
mal a given individual's blood is. When a given disease like 
pneumonia occurs, we need to know, if possible, what is the ordi- 
nary leucocyte count and differential count of that case, on top of 
which a leucocytosis may (or may not) be built up. 

Condition of stasis, temporary blood concentration, dilution, and 
vasomotor disturbances must, of course, be excluded or allowed for, 
since these may increase not only the total leucocyte count, but 
often the percentage of polymorphonuclear cells. Whether or not 
differences of race make any difference in the normal count of white 
cells, I cannot say, but certainly the average of a group of college 
athletes would be higher than that of some country towns in Is"ew 
England where everybody is more or less under-nourished ; and if 
one is to practise among all sorts and conditions of men, I think he 
cannot but expect to find people's leucocytes vary all the ^V3,J from 
5, 000 to 10, 500 per cubic millimeti'e, without there being more than 
malnutrition to account for the lower figures. 

We may divide leucocytoses for convenience' sake into : 1. Phy- 
siological leucocytoses. 2. Pathological leucocytoses. 



LEUCOCYTOSIS. 



97 



Physiological Leucocytoses. 

1. Leucocytosis of the new-born. 

2. Leucocytosis of digestion. 

3. Leucocytosis of pregnancy. 

4. Leucocytosis post partum. 

5. Leucocytosis after violent exercise, massage, and cold baths. 

6. Leucocytosis of the moribund state. 

The Leucocytosis as Affected hy Digestion. 

{a) Total abstinence from food lowers the leucocyte count. In 
the blood of the professional faster Succi, the number sank within 
his lirst week's fast to 861 per cubic millimetre. After the first 
week it rose to 1,530, and remained there throughout his thirty 
days' abstinence (Luciani).' The polymorphonuclear cells and 
eosinophiles are said by Tauszk to be increased in chronic starvation. 

Von Limbeck counted the blood of a melancholic patient who 
had fasted a week, and found 2,800 white cells per cubic millimetre. 
These facts support the idea that the number of leucocytes depends 
(within certain limits) on the individual's assimilation of food. In 
cancer of the gullet we find similar low figures. 

(h) After a meal rich in proteids the leucocyte count rises about 
thirty -three per cent in most sound persons. Ten thousand cells 
may perhaps be considered the average, three to four hours after a 
proteid meal, but if the count before a meal is only 4,000 or 5,000, 
digestion will perhaps not raise it above 7,000, while vigorous adults 
may show 13,000. Digestion leucocytosis is always relative to the 
count of the individual's blood tvhen fasting. This is to be ob- 
tained preferably before breakfast, as during the day the leucocyto- 
sis caused by one meal may not be gone before the influence of the 
next meal begins. Examples of digestion leucocytosis in diseases 
other than gastric are seen in the following table : 



Case. 


Diap^nosis. 


Count before 
food. 


Count after 
food. 


1 




10,000 
10,400 
7,500 
5,450 


18,900 
21,700 
13,500 
8,650 


2 




3 


Neurasthenia 


4 


Adhesions around gall-bladder. 





^"Das Hungern," German translation by O. Frankel. Hamburg, 1890. 

7 



98 



CLINICAL BLOOD EXAMINATION. 



Occasionally we see sound persons with little or no digestive 
leucocytosis. Some of these cases are to be explained by habitual 
constipation (v. Limbeck) ; in others the reason is more obscure. 
But there is no doubt of its being the rule after meals of mixed or 
proteid diet. 

Any disease of the gastro-intestinal tract, whether functional or 
organic, may prevent the appearance of the digestion leucocytosis 
(see later under Diseases of the stomach, page 293). In anaemic 
and debilitated conditions it is frequently absent. 

In children it is especially marked. Schiff ' records a case of a 
healthy infant whose blood an hour after birth showed 19,500 (see 
next section), after its first meal 27,625, and after its fourth meal 
36,000 white cells per cubic millimetre. After the second day this 
gradually diminished. 

Food seems to call forth a greater leucocytosis in proportion as 
it is a novelty in the stomach. Patients with gastric ulcer who had 
been fed exclusively by rectum for some weeks show a greater leuco- 
cytosis after their first meal than later. Perhaps the size of the 
digestion leucocytosis in the new-born is to be similarly explained. 
In diabetics the digestion leucocytosis is sometimes very large. 

The leucocytosis can usually be observed one hour after a meal, 
increases for two, three, or even five hours according to the slowness 
of digestion, then falls again. 

Burian and Schur- found an increase of the polymorphonuclear 
varieties in those cases in which an increase of the total count took 
place at all. Rieder reports a lymphocytosis. It is probable that 
both lymphocytes and neutrophiles are increased, while eosinophiles 
are reduced. 

Diagnostic Value. 

1. When we wish to know whether a person is accurate in such 
statements as that they have ''eaten nothing for a week," we can get 
evidence from the leucocyte count, which should be very low if the 
assertion be true. Whenever we cannot communicate with a patient 
and wish to know how much food he has taken of late, we can form 
some idea from the blood examination. In the case of a patient 
who spoke only Russian, I was led to look for a stenosis of the gul- 
let by the lowness of the leucocyte count (2,700), and the probang 
confirmed the suspicion. 

'Zeit. f. Heilk., xi., 1890. 

'-^Wien. khn. Woch., February 11th, 1897. 



LEUCOCYTOSIS. 



99 



2. As suggested above, we can form some idea of a person's 
general vigor, nutrition, and capacity to assimilate food by the 
number of leucocytes and the proportion of mononuclear cells, as 
compared with the average figures for that age and locality. Per- 
sons debilitated from any reason are apt to show it in their blood 
by the changes above mentioned, the element of hysteria being 
sometimes recognizable by other signs (see below ^^Eosinophilia," 
page 115). 

3. Slowness of digestion is indicated by a late appearance of the 
digestion leucocytosis. The inferences to be drawn from the blood 
in diseases of the gastro-intestinal tract Avill be discussed later (page 
298). 

4. Perhaps the chief importance of digestion leucocytosis is as a 
possible cause of false inferences, through being taken for a patho- 
logical increase. Bearing this in mind, we must always examine 
the blood as near a meal as possible, or better still before breakfast. 

Leucocytosis of the Neiv-Born. 

The following table is compiled from the best authorities on the 
subject (Schiff, Gundobin, Bayer, Hayem, and others) : 



Age. 

At birth 

End of first day 

" second day 

" fourth day 

" seventh day 

Tenth day 

Twelfth to eighteenth day 

Sixth month \. 

Sixth year and upward . . . 



Red cells. 



5,900,000 



7,000,000 to 8,800,000 
Generally increased. 

6,000,000 

5,000,000 



Leucocytes. 



17,000 to 21, 000(26,- 
000 to 36, 000 after 
first feeding) . 
24,000 
30,000 
20,000 
15,000 
10,000 to 14,000 
12,000 
12,000 
7,500 



The increase is explained by Lepine, v. Limbeck, and others as 
a combination of blood concentration with large digestion leucocy- 
tosis. Gundobin and others are opposed to this theory. Certainly 
the influence of digestion on infants' blood is much greater than in 
adults. After a meal 30,000 leucocytes is never a very high count 
in infants under two years. 

A fuller discussion of the subject will be found in the chapter 
on the blood in infancy. 
LorC. 



100 



CLINICAL BLOOD EXAMINATION. 



TJie Leucocytosis of Pregnancy. 

Most primijxn'ce show during the later months of pregnancy a. 
moderate increase of all varieties of leucocytes. Thirteen thousand 
cells per cubic centimetre is about the average count. 

In multiparse it occurs in only about fifty per cent of the cases. 
Digestion leucocytosis " on top of " the constant pregnancy leucocy- 
tosis, so to speak, rarely occurs. 

As mentioned above, the relative percentage of the different 
types of leucocyte remains unchanged, so that all varieties must be 
equally increased (eosinophiles excepted). The fact that digestion 
does not increase the pregnancy leucocytosis, leads to the suggestion 
that the whole thing may be only a prolonged digestion leucocytosis 
— the mother having to eat for two. The swelling of the breasts 
may also account for part of the leucocytosis. In the last weeks 
of pregnancy the leucocytosis increases till at the beginning of labor 
it is often 16,000 to 18,000. It has no diagnostic value, as it is not 
present during the earlier months of pregnancy when diagnosis is 
difiB.cult, and in the later months such conditions as hydatidiform 
mole and fibroid tumors might raise the count of white cells as much 
as pregnancy. 

Leucocytosis After Parturition. 

The following charts illustrate the course of the leucocyte curve 
from the time of parturition till the end of the second week after it. 

All were primiparse excepting Nos. 5, 8, and 9. There was no 
sepsis in any case, and the temperature charts were practically nor- 
mal after the second day. No reasons are known for the variations 
between the different cases. All were counted at the same hour of 
the day, and under the same conditions of nutrition. All nursed 
their children. 

The only importance of this leucocytosis is that it might be con- 
founded with a pathological leucocytosis in a case suspected of being 
septic. Just how long the leucocytosis is prolonged during lactation 
has not been studied so far as I am aware, but it certainly may go 
on several weeks. 

Violent exercise, massage, and short cold baths have been shown 
to cause a temporary increase in the number of leucocytes in the 
peripheral blood, all varieties of the cell being equally increased. 
The explanation usually given is that the blood is concentrated by 
vasomotor contraction and rise of blood pressure. 



LEUCOCYTOSIS. 



101 



Schultz {Dent. Arch. f. Mm. 3Ied., 1893, page 234) found the 
leucocytosis of exercise amount to about the same as that of diges- 

o o o o o 
SoSoooo 



i 



a a 



5? ^ 



tion, 11,000 to 13,000. He also noted that in dogs merely opening 
the peritoneum aseptically or breaking a leg caused leucocytosis/ 

'Blake (Annals of Surgery, 1901) reports on the blood of runners In a 
recent "Marathon race " as follows : The leucocytes rose from 7,000 to 10,000 
before the race to 18,000 to 21,000 after it. The polynuclear cells were in- 
creased and eosinophiles absent. After fractures Blake and Hubbard found 
no increase in leucocytes. 



102 



CLINICAL BLOOD EXAMINATION. 



Thayer studied twenty cases of ty2:>hoid and found an average 
of 7,724 white cells before and 13,170 after a Brand bath {Johns 
IlopJdns Medical Bulletin, April, 1893). The increase took place 
equally in all varieties. Winternitz (Iniperio-Eoyal Medical So- 





ciety, Vienna, February, 1893) came to a similar conclusion and 
found also that prolonged cold bathing decreased the number of 
white cells (dry cold does the same). A patient was recently 



LEUCOCYTOSIS. 



103 



brought to the Massachusetts Hospital who had fallen through a 
hole in the ice and been some minutes in the icy water. His tem- 
perature was 91.8° by the rectum. Blood count showed 17,500 
leucocytes per cubic millimetre. J^ext day he was perfectly well. 
On the contrary, short hot baths decrease and prolonged ones in- 
crease the number of leucocytes. 

Local arm baths have a similar effect, raising the count of leu- 
cocytes in the blood of the immersed arm if cold and short, and 
lowering it if hot and short, while prolonged immersion has an op- 
posite effect. In the other arm the counts go up when those of the 
immersed arm go down, and vice vei^sa (Rovighi).^ Mitchell ^ found 
that the leucocytes showed distinct increase (as well as the red cells 
and hsemoglobin) after one hour's general massage. 

All these forms of leucocytosis are usually explained by changes 
in blood pressure, and vasomotor changes affecting the calibre of the 
peripheral vessels and consequently their contents. 

Tennina I Leucoc ijtos is. 

The leucocytosis of the moribund state, though by no means in- 
variable, occurs in many cases, whether from the influence of a ter- 
minal infection or from stasis. When death is sudden or rapid it 
does not occur. It seems to be analogous to the terminal rise of 
temperature seen at the close of many chronic non-febrile affections. 
The longer the patient is moribund the higher the count reaches. 
In pernicious anaemia the increase may be so great as to simulate 
lymphatic leukaemia. Such a case occurred in the writer's own ex- 
perience. The patient had presented the signs and symptoms of 
pernicious anaemia, and the blood was typical of the disease in all 
respects except for the lack of nucleated red cells. 

Slides taken on the day of death showed a ratio of one white to 
fifteen red cells, the small lymphocytes greatly predominating, but 
the autopsy revealed simply the lesions of pernicious anaemia. The 
differential count of one thousand leucocytes on the day of death 
showed: Lymphocytes, 91.7 per cent; polymorphonuclear cells, 7.7 
per cent; eosinophiles, 0.5 per cent. Four megaloblasts were seen 
while counting these. The total leucocyte count was unfortunately 
not made. 

In ordinary cases the differential count shows an increase m the 

' An-h. Ital. d. CHn. Med., xxxii., 3, 1893. 

'- American Journal of the Medical Sciences, May, 1894. 



104 



CLINICAL BLOOD EXAMINATION. 



polymorphonuclear leucocytes. Thus m a case reported by Eieder, 
in which the leucocyte count rose during the last two days of life 
from 7,800 to 59,300, the polymorphonuclear cells constituted 87.5 
per cent of the whole 59,300. 

Pathological Leucocytoses. 

For convenience' sake these may be divided as follows : 

1. Post-hemorrhagic leucocytosis. 

2. Inflammatory leucocytosis. 

3. Toxic leucocytosis. 

4. Leucocytosis in malignant disease. 

5. Leucocytosis due to therapeutic and experimental influences. 

1. Post-liemorrhagic Leucocytosis. 

Within an hour after a large hemorrhage we find commonly a 
considerable increase (16,000-18,000). In hemorrhage from the 
stomach this disappears again usually within a day or two, while in 
ordinary traumatic hemorrhage it persists longer. This last fact 
may perhaps be explained, as v. Limbeck suggests, by the local 
conditions in the wound rather than by the loss of blood in itself. 

The polymorphonuclear leucocytes are usually increased rela- 
tively and absolutely as in other forms of pathological leucocytosis. 
Sometimes we have lymphocytosis (see page 114). The average of 
increase in the white cells is parallel in a general way to the anaemia 
produced in the individual, i.e., it depends on his powers of recu- 
peration rather than on the amount of blood lost. Its duration fol- 
lows the same rule.^ 

2. Inflammatory Leucocytosis. 

I use the term "inflammatory leucocytosis " rather than "leuco- 
cytosis of infectious diseases " because there is a considerable number 
of infectious diseases in which no leucocytosis occurs, while it ac- 
companies almost all forms and cases of inflammation. Keverthe- 
less I shall class under this heading some diseases in which inflam- 
mation plays but a very subordinate role. 

I. Although purulent and gangrenous processes usually cause 
a higher count of white cells than serous processes, the amount of 
the exudation is not a measure of the amount of leucocytosis. It 

^ Further account of the blood after hemorrhage will be found on p. 126 
et seq. 



LEUCOCYTOSIS. 



105 



seems to depend rather on the resultant of two forces, viz., the 
severity of the infection and the resisting power of the individual. 
These factors may interact in various ways : 

1. Infection mild : resistance good = small leucocytosis. 

2. " less mild : " less good = moderate leucocytosis. 

3. " severe : " good = very marked leucocytosis. 

4. " " " poor = no leucocytosis. 

This will be illustrated later under "Pneumonia" and under 
"Sepsis." Experiments on animals show that whereas moderate- 
sized doses of septic cultures, not sufficient to kill the animal, are 
followed by leucocytosis, larger doses after which death follows 
speedily, do not raise the leucocyte count at all. Animals weak- 
ened by any cause show less leucocytosis to a moderate dose than 
strong animals. 

If the individual reacts from the shock his leucocytes are in- 
creased again and rise above normal. If reaction fails the leuco- 
cytes do not rise. 

II. Inflammatory leucocytoses differ from physiological leucocy- 
toses — 

(a) In being usually of larger extent and greater duration. 
{h) In being almost always accompanied by a relative and abso- 
lute increase in the percentage of polymorphonuclear cells. 

III. The course of the leucocytosis as regards both amount and 
duration shows, like the temperature chart, certain more or less 
characteristic differences in different diseases. 

IV. In some cases in which the absolute number of leucocytes 
is not increased, we see a relative increase in the polymorphonu- 
clear cells, pointing to the fact that influences are at work similar 
to those which produce an absolute increase. 

V. That the amount of exudation is not of itself a measure of 
the amount of leucocytosis is shown by the fact that erysipelas or 
scarlet fever may be accompanied by as high a count as the average 
count in pneumonia or empyema. 

That purulent exudations usually have more effect on the white 
cells than do serous ones is due, I suppose, to the fact that a puru- 
lent inflammation usually means a severer infection. 

VI. No direct connection exists between leucocytosis and fever, 
many febrile affections running their course with a normal leucocyte 
count. When both leucocytosis and fever are due to the same 



0 



CLINICAL BLOOD EXAMIXATIOX. 



causes they rise and fall together, hut the correspondence is rarely 
accurate, and marked leucocytosis may exist without fever. 

YII. Acute, rapidly sprt^ading inilammatious seem to produce a 
greater leucocytosis (other things being equal) than those m which 
the process is relatively rhronic and stationary. For instance, an 
appendicitis, when well walled off and statioiiary, shows less in- 
crease in white blood cells than while it> lesions are progressing. 
But peracute, overwhelming general sepsis may ha^'e no elfect 
on the leucoc}i:es, the reactive power of the organism being 
crushed. 

VIII. Most inflammatory leueocytoses are preceded by a tem- 
porary diminution in the number of leucocytes. This occurs in 
animals from sltocl' of any kind (blows on the head, tying to the 
etherizing board), and it seems not unlikely that the cause is the 
same in all cases. 

The following is a list of the more important inflammatory or 
infectious conditions in which leucocytosis appears : 

1. Infectious diseases icitli comijaraticely s^i'jJit loral IriMo. mmntory 
processes : 

(a) Asiatic cholera. 
(I)) Relapsing fever. 

(c) Typhus fever (according to the majority of observers). 
((/) Scarlet fever. 

[e) Diphtheria and follicular tonsillitis. 

(f) Syphilis (secondary stage) . 
[(/) Erysipelas. 

(h) The bubonic plague. 

(i) A^ellow fever (some cases). 

2. In fectioiis disecsi's vifli more extensive local lesions : 

[a) Pneumonia. 

[b) Smallpox (suppurative stages 

[c) Malignant endoearditi>, puerperal septicaemia, and all pytemic 
and septica?mic conditions. 

{d ) Actinomycosis. 
(e) Trichinosis. 
if) Glanders. 

( r/) Acute multiple neuritis (febrile stages) . 

(h) Acute articular rheumatism. 

(i) Septic meningitis and cerebro-spinal meningitis. 

(j) rholangiti>. cholecystitis, and empyema of the gall bladder. 



LEUCOCYTOSIS. 



107 



Acute pancreatitis. 
(/) Endometritis, cystitis (some acute cases). 
(m) Gonorrhoea. 

3. Local inffam inafoi'f/ proressej-^ : 
^ (a) Abscesses of all kinds and situations, such as 
Felon. 

Carbuncle, furunculosis. 

Tonsillar and retroj^haryngeal abscess. 

Appendicitis, phlebitis (some cases). 

Pyonephrosis, perinephritic abscess, and pyelonephritis. 

Osteomyelitis, empyema. 

Psoas and hip abscess when not simply tuberculous. 
Abscess of lung, liver, spleen, ovary, prostate. 
Salpingitis and pelvic peritonitis, epididymitis. 
(/>) Injiammafloiis oftlie serous membranes including: 
Pericarditis, peritonitis, arthritis (serous or purulent, non-tuber- 
culous) , conjunctivitis. 

(c) Gangrenous inflammations, as of the 
Appendix, lung, bowel, mouth (noma). 

((/) Many inflammatory skin diseases, such as dermatitis, pem- 
phigus, pellagra, herpes zoster, prurigo, some cases of universal 
eczema, etc. 

S. Toxic Leucorj/tosis. 

Under this heading I have grouped most of the conditions not 
obviously to be explained as infectious or inflammatory (though 
some may turn out to be such) and not due to malignant disease or 
therapeutic agencies. This classification is chiefly for convenience' 
sake and represents only a guess at the real explanation of the leu- 



cocytosis : 






{a) Leucocytosis of illuminating-gas poisoning. 


(?') 


a 


" quinine poisoning. 


('■) 


u 


" rickets (many cases). 


(rf) 


(( 


" the uric-acid diathesis, gout. 


(") 


i( 


" acute yellow atrophy of the liver. 


(/) 


u 


" advanced cirrhosis of the liver (some cases), 






especially with jaundice. 


in) 


(( 


" acute gastro-intestinal disorders (pto- 






mains?). 


(h) 


a 


" chronic nephritis, usually in uraemic cases. 



108 



CLINICAL BLOOD EXAMINATION. 



(I) Leucocytosis after injections of tuberculin and thyroid ex- 
tract. 

(J) after injection of normal salt solution (intra- 

venous). 

(k) " after ingestion of salicylates, potassium chlor- 

ate, or phenacetin. 

(I) " during and after prolonged chloroform narcosis. 

Zerber (Inaug. Dissert., Berne, 1896) found the leucocytes in- 
creased after etherization in 96 out of 101 cases examined. The 
increase amounted in 35 cases to double and in 23 to triple the count 
before ether. 

In no case was the count made after etherization and before the 
operation was begun, so that it is impossible to say how far the leu- 
cocytosis was due to ether. Since it has been shown that in animals 
a leucocytosis can be produced simply by opening the peritoneum, 
or even by the shock of tying the animal to the operating table, it 
is essential to rule out the effects of the operation itself. 

In Chadbourne's careful study of 21 cases {FJiil. lied. Jovrn.^ 
February 18th, 1899) counts were made just before etherization and 
then after full narcosis, but before the operation was begun. Di- 
gestion leucocytosis was excluded. Every case showed an increase, 
the average gain being 37.3 per cent. The increase is exceedingly 
rapid, some cases showing a change of 70 per cent within a few 
minutes; it is most marked in the first part of etherization. The 
degree of leucocytosis did not seem to depend on the duration of 
narcosis. 

Differential counts showed that all varieties of leucocytes were 
increased — the lymphocytes slightly more than the others. 

Chadbourne considers the leucocytosis due to the irritation of 
the ether vapor upon the mucous membrane of the respiratory tract. 

Blake and Hubbard in a study of 28 cases before and after full 
ether ansesthesia, found no considerable increase in the circulatory 
leucocytes {Annals of Surg erij^ 1901). 

Possibly the leucocytosis of acute ddwiiim. belongs also in this 
group. 

^. LpAicocytosis of Malignant Disease. 

Very likely this belongs more properly under one or another 
of the classes just mentioned. Some observers think that it occurs 
only from the inflammation excited m the periphery of some malig- 



LEUCOCYTOSIS. 



109 



naiit tumors ; others that it is due to absorption of morbid products 
from the tumor itself ; others again that it is to be accounted for by the 
cachectic state associated with the growth of the tumors. The details 
and conditions of its occurrence will be discussed later (page 370). 

5. Leucoc tjtosls Due to TJierapeidic and Experimental InfiiLences. 

Pohl ' found that most of the so-called tonics and stomachics 
produce a slight increase in the white cells in animals, particularly 
the vegetable tonics like tincture of gentian, and oil of anise seed, 
while bismuth, bicarbonate of soda, and iron had no such effect. 
Quinine, caffeine, and ethyl alcohol gave likewise negative results. 
Von Limbeck found leucocytosis in men after oil of peppermint and 
oil of anise seed. 

Binz' got the same results with camphor. In all these experi- 
ments the substances were given by the mouth. 

Using subcutaneous or intravenous injections, Lowit experi- 
mented on animals with hemialbumose, peptone, pepsin, nucleinic 
acid, nuclein, extract of blood-leech, pyocyanin, tuberculin, curare, 
uric acid, urate of sodium, and urea. All but the last of these 
produce temporary decrease followed by increase of leucocytes. 

Goldschneider and Jacob ^ used extracts of various organs. Ex- 
tract of spleen, marrow, and thymus produced leucocytosis pre- 
ceded, as in Lowit' s experiments, by a brief diminution in the num- 
ber of leucocytes, while extract of pancreas, thyroid, kidney, and 
liver had no effect. 

Winternitz* injected a large variety of substances subcutaneously 
and found that the degree of leucocytosis was parallel to the degree 
of local reaction excited. 

For example, neutral salts and weak acids or alkalies produced 
slight local inflammation and a leucocytosis of from forty to seventy- 
five per cent of the original count. But irritants like turpentine, 
croton oil, nitrate of silver, sulphate of copper, mercury, antimony,- 
digitoxin, etc., produced local suppuration (aseptic) and much 
greater leucocytosis (two hundred to three hundred per cent). 

Pilocarpine and antipyrin have been found by von Jaksch and 
others to produce marked increase in the number of leucocytes when 

'Arch. f. exp. Path. u. Pliarm., 1899, vol. xv. 
^Arch. f. exp. Path. u. Pharm., vol. v., p. 122. 
3 Arch. f. Anat. u. Physiol., 1893, p. 567. 
^Arcli. f. exp. Path. u. Pharm., vol. xxxv., p. 77. 



110 



CLINICAL BLOOD EXAMINATION. 



given subcutaneoiisly. During the use of thyroid extract Richter 
{Centralhlatt f. inn. Med., 1896, p. 3) noted leucocytosis. Kenzi 
and Boeri report leucocytosis (slight) after purgatives such as castor 
oil, podophyllin, and scamniony. 

A large number of observations on the effects of injections of 
bacteria or their toxins agree in the following results : 

1. When the dose is very large the leucocytes are reduced, and 
the animal dies. 

2. When the dose is not sufficient to kill the animal the tem- 
porary dimmution in the leucocytes is soon followed by leucocytosis. 

3. When the dose is slowly fatal the count of leucocytes oscil- 
lates up and down within wide limits. 

4. Animals previously rendered immune to the poison injected 
show little or no leucocytosis. 

5. Leucocytosis is more easily called forth and of greater extent 
in young animals. 

6. Most pathogenic organisms act similarly, but bacilli and' 
toxins of tuberculosis as a rule cause no leucocytosis. 

7. There is no evidence that any one variety of leucocyte is at- 
tracted by any particular bacillus or toxin. 

In the above sketch of therapeutic and experimental forms of 
leucocytosis no attempt has been made to give anything but the 
more interesting and important outlines of the immense amount of 
Avork done. 

Cell Structure of the Leucocytes in Leucocytosis. 

Hitherto we have spoken as if leucocytosis meant only an in- 
creased number of the normal cells, but one cannot study the cell 
forms in extensive pathological leucocytosis without noting in many 
cases qualitative changes in the individual cells. These are chiefly: 

1. A greater or less approximation of the nuclei of polymorpho- 
nuclear neutrophiles to the appearances of the myelocyte nucleus. 
As will be mentioned later under leuksemia, we find in every blood 
containing many myelocytes numerous cells whose nucleus is on the 
border-line between the myelocyte and the polymorphonuclear stage, 
so far as appearances go. Now in leucocytosis we find the same 
" border-line " cells in smaller numbers, the likeness to the myelocyte 
sometimes passing into identity in one to three per cent of the cells. 

2. Ttirck's " Eeizungsf ormen " or "stimulation-cells" in which 
the protoplasm of the cell (which is in other respects like a large 



LEUCOCYTOSIS. 



Ill 



lymphocyte) shows a greater or less approximation to the appearance 
of myelocyte protoplasm, i.e., a diffuse violet or purple color ex- 
actly as in the myelocyte but non- granular. Engel makes a separate 
variety of this cell, giving it the useless name of "mononuclear 
cell. " Weil calls it the " non-granular myelocyte. " Ttirck considers 




Fig. 28,— Atypical Leucocytes seen in Leucocytosis. 1, Leucocytes with polar arrangement of 
nuclei (mitosis ?); 3 and 3, leucocytes with nuclei resembling those of myelocytes ; 4, leu- 
cocyte containing two kinds of granules. 

its presence in the circulating blood to indicate a stimulation of the 
marrow by the toxins of disease, resulting in the passage of this — 
supposedly immature — cell into the blood. 

3, Other finer changes, such as the number, size, and staining 
power of the neutrophilic granulations, polar position of the nuclei, 
etc. (see Fig. 28), require further study. 

Changes like the above militate against the idea that leucocyto- 
sis is simply a matter of the distribution of fully formed leucocytes 
in the peripheral or internal vessels. 

For an account of iodophilia or the iodine reaction in the poly- 
nuclear leucocytes during suppurations see p. 239. 

Absence of Leucocytosis. 

It is of fully as great a practical assistance to us to know that in 
certain infective diseases leucocytosis is regularly absent as to know 



112 



CLINICAL BLOOD EXAMINATION. 



those conditions in which it is to be expected. Among the most 
important diseases in which leucocytosis is conspicuously absent 
are : 

(a) Typhoid fever. 

(b) Malaria. 

(c) Grippe (most cases) . 

(d) Measles. 

(e) E-otheln and mumps. 
(/) Cystitis. 

( gf) Tuberculosis, including — 
Incipient phthisis. 
Miliary tuberculosis. 
Tuberculous peritonitis. 

" ostitis and periostitis. 
" pleurisy. 
" pericarditis.' 
In some of these affections, notably in miliary tubercle and the 
later weeks of typhoid, the leucocytes are diminished. Further de- 
tails will be given under the special diseases. 

Leucopenia. 

Definition. — A diminution in the number of white cells in the 
peripheral circulation as compared with the number normal for the 
given individual. 

1. The effects of starvation and malnutrition in producing leuco- 
penia have already been described. Such leucopenia is usually as- 
sociated Avith lymphocytosis (see below). Cancer of the gullet is 
an example of this class. 

2. Short hot baths or prolonged cold baths produce temporarily 
the same result (Winternitz, loc. cit.). 

3. Most of the infective diseases in which there is no leucocyto- 
sis are sometimes characterized by leucopenia, e.g., grippe, measles, 
miliary tuberculosis, and other forms of pure tuberculous infection, 
malaria, and especially typhoid, in the later weeks of which it is 
almost invariable, and is accompanied by lymphocytosis. 

When a case of leukaemia is complicated by an infective disease 
(pneumonia, septicaemia) the number of leucocytes may fall below 
the normal. In a case recently occurring at the Massachusetts 



' Tuberculous meningitis often does show leucocytosis {vide infra, p. 282). 



LYMPHOCYTOSIS. 



113 



General Hospital in which a lymphatic leukaemia was terminated by 
septicaemia from glandular suppuration, the white cells fell grad- 
ually from 40,000 three weeks before death to 419 per cubic milli- 
metre on the day of death. I have never heard of a lower count 
than this. The differential count was unchanged (lymphocytes = 
ninety-eight per cent). 

4. In pernicious anaemia the count is usually very low and may 
fall below 1,000 cells per cubic millimetre. Other severe types of 
anaemia (rachitic, syphilitic, post-hemorrhagic) may produce the 
same result. 

5. Splenic anaemia or the splenic form of Hodgkin's disease is 
often associated with marked leucopenia. 

Lymphocytosis. 

Lymphocytosis is an absolute and relative increase in the circa- 
lating lymphocyfes. The increase is relative to the number of 
lymphocytes normal for the individual. When lymphocytosis and 
an increase of the total leucocyte count are present we cannot 
distinguish the blood from that of lymphatic leukaemia, and the 
distinction must depend upon the course and symptoms of the 
case. 

1. Such a condition (relative to the adult) occurs in healthy in- 
fants'' blood and in many diseases of infancy, the blood seeming to 
have a tendency to return to the infantile type. This is especially 
true of cholera infantum, rickets, and any intestinal trouble. Any- 
thing that retards the infant's normal gain in weight or general de- 
velopment retards its blood development as well. Thus a child of 
three, convalescent from a summer diarrhoea, may have fifty to sixty 
per cent of lymphocytes, which would be normal for an infant of a 
few weeks, but for three years old is very high. 

2. Pertussis, as Meunier has recently shown, is accompanied by 
a very marked lymphocytosis, the lymphocytes being quadrupled 
while the polynuclear cells are doubled. The increase is absolute 
as well as relative (see below, page 218). 

Variola also shows lymphocytosis according to Weil. 

3. Hereditary syphilis is perhaps the best known cause of rela- 
tive lymphocytosis in children. Scurvy may produce the same re- 
sult. Dividing the anaemias of children into two groups, those that 
do and those that do not produce leucocj^tosis, it appears that the 

8 . 



114 



CLINICAL BLOOD EXAMINATION. 



great majorit}' of those whose total leucocyte count is normal show 
a relative lymphocytosis. This is the case irrespective of whethei 
there is enlargement of the spleen or not. 

Sometimes the smaller, sometimes the larger lymphocytes are in 
the majority. Often no division between the two kinds is pos- 
sible. 

4. In adults some forms of dehUiti/ may be associated with an 
increased percentage of lymphocytes, due in fact to the absolute 
dlu) i II iituni of the iieiftrop// i/es. This should be distinguished from 
true lymphocytosis. The same false appearance of lymphocytosis 
may be seen in hgemophilia, goitre, cervical adenitis, and other 
conditions involving a diminution of the polynuclear neutrophiles, 
ill chlorosis, j/eni icioiis aiupiiiki, Graces' disease, and the anaemia 
secondary to s////h ilis, in the later weeks of typhoid fever and in 
lactation. 

o. During the administration of thyroid extract, tuberculin, or 
pilocarpine. • 

6. The larger forms of lymphocytes are increased in some splenic 
tumors (chronic "ague cake"), and especially in the post-febrile 
stage of measles ; also in many of the same diseases in which the 
small lymphocytes are increased. 

7. The most marked absolute lymphocytoses known to me (ex- 
cluding leukaemia) occurred in two cases of pertussis-pneumonia in 
infancy. One case occurred at the Massachusetts General Hospital 
in 1894 — in a child of six, who passed through an attack of broncho- 
pneumonia with uneventful recovery, the only peculiarity of the 
case being the marked increase of white cells running up to 94,600, 
shty-nine per cent of which irere ri/nipJiocj/tes. During convalescence 
the blood became normal and the child left the hospital entirely 
well. In 1900 we had a similar case in a baby of fifteen months, 
well until seized with paroxysms of coughing four days before en- 
trance. The spleen and glands were normal. There were no hem- 
orrhages and no anaemia. The blood showed 





White cells. 


Per cent 
polynuclear. 


Per cent 
lymphocytes. 


Per cent, 
eosinophiles. 


Remarks. 


First day . 
Third day. 
Fifth day . 
Sixth day. 


108,000 
104,850 
185,000! 
Death. No 
autopsy. 


35 


64.5 


0.5 


Red cells normal. 
No nucleated forms. 



EOSIXOPHILIA. 



115 



Since reading Meunier's account of the enormous lymphocytosis 
of wlwopin(j-vou(jl) I have believed these two cases to have been 
atypical whooping-cough. These cases will be referred to later 
in the account of the blood of pneumonia. 

Dlajjiiostlc Value of Lijmpliocytosis. 

1. 1 have already suggested that the degree of health in persons 
not organically diseased might perhaps prove to vary directly with 
the percentage of polymorphonuclear cells in the blood. 

2. In children the same percentage is to a certain extent a meas- 
ure of the child" s degree of development — causes of leucocytosis 
being excluded, and the percentage normal for a child of the pa- 
tient's age being taken as the standard. 

3. The diagnosis of obscure sy^^hilitic disease may be supported 
by the coincidence of lyniphocyi^osis with eosinophilia. 

4. Absolute lympliocytosis in the presence of glandular tumors 
is our mainstay in the diagnosis of lymphatic leukaemia, but whoop- 
ing-cough must always be remembered as a source of error. 

EOSIXOPHILIA. 

Definition. — An increase in the number of eosinophiles in the 
circulating blood. 

PJi ijsiolocjieal Eosinoph ilia. 

1. In the majority of infants the eosinophiles are much more 
numerous than in adults, Taylor has noted as many as 2,200 per 
cubic millimetre in healthy babies. 

2. A temporary increase occurs during menstruation (eight per 
cent, Zappert). 

Among the causes ol patliologicaJ eosinophilia are: 

1. Bronchial Asthma and Fibriiious BroncJiitis. — During par- 
oxysms the eosinophiles are plentiful in the sputum and in the 
mucous membrane of the upper air passages as well as in the blood. 
In the case quoted from Billings (see below, p. 340) there were 53 
per cent of eosinophiles in a leucocyte count of 8,300. Gabrit- 
schewsky reports 22.4 per cent in asthma. 

2. Acute and Chronic Skin Diseases. — The most marked cases 
are those reported by Lazarus (60 per cent of eosinophiles in tc7'ti- 
caria (widely distributed), Zappert (33 per cent, or 4,800 eosino- 
pMles per cubic millimetre in pemphigus), and by Canon (17 per 



116 



CLINICAL BLOOD EXAMIXATION. 



cent in jDrurigo and psoriasis). In (hr/z/ntitis Jieqjt^tlforinls high 
eosinophile counts are re^^orted by Leredde and Perrin, by Brown, 
and by myself (see below, p. 442;. 

3. Helm int/i icsis. — Trich inosis and (inJc[/h)Stoin uis'is are the mem- 
bers of this group which have been most thoroughly studied, and 
in both of them eosinopliilia is marlved and constant (see pages 434 
and 428 ). 

Bucklers working under Leichtenstern has established the in- 
teresting fact that o.U varieties of helminthides from the harmless 
oxyurides to the pernicious ankylostoma may bring about an increase 
of eosinophiles in the blood, often to an enormous extent. Biicklers 
re^^orts 16 per cent of eosinophiles in oxyurides. and 19 per cent in 
ascarides, and Leichtenstern has quite recently found 72 per cent of 
eosinojjhiles in ankylostomiasis and 34 per cent in a case of taenia 
mediocanellata (Ehrlich and Lazarus, p. 429). 

4. Post-F^'hrU^:. — At the height of most acute infectious fevers 
(except scarlet fever and sometimes rheumatic fever) the eosino- 
philes are greatly diminished or absent. In the post-febrile period, 
however, abnormally higli percentages of eosinophiles are often 
found. 

Tiirck found 5. 67 per cent (430 absolute) after pneumonia; 13.8 
and 9.37 per cent (970 absolute) after rheumatism. Zappert found 
20.34 (1,486 absolute 1 after malaria : 26.9 per cent (3.220 absolute) 
after tuberculin reaction fever. Grawitz f oimd 90 per cent ( I) 
(41,000 absolute) after tuberculin reaction fever (see page 272"). 

5. Mcdkfnant Tuniors. — Various authors (AVeiss. Palma, Eieder) 
have observed a slight eosinophilia in connection with the cachexia 
of malignant disease. It is, however, of moderate degree and 
seldom exceeds 7-10 per cent. 

In Eeiiibach's study of 40 cases there were 4 with eosinophilia 
a.s follows: Sarcoma of the forearm, eosinophiles 7.8 per cent; 
sarcoma of the femur, eusinophiles 8.4 per cent; malignant tumor 
of the abdomen, eosinophiles 11.6 per cent ; lympho-sarcoma of neck 
with ulcerative endocarditis and metastases in the bone marrow, 
eosinophiles, 48 per cent (60.000 absohite). see p. 368. 

Among my cases there is one of generalized sarcoma with eosino- 
philes 12.4 (2.108 absolute). Zappert quotes a case of lympho- 
sarcoma with 17.7 |>er cent (2.077 absolute) and 2 cases of cancer 
(uterus and stomach) with 11 per cent (860 absolute) and 8.5 per 
cent (535 absolute). 



EOSINOPHILIA. 



117 



6. Co)upensatonj Eos'niojjhUla. — Ehrlich's researches appear to 
show that when the function of the spleen is abolished, either by 
splenectomy or by disease, a late compensatory eosinophilia occurs. 

7. Medicinal Eosinophilia. — After the administration of cam- 
phor, V. ^^oorden observed an eosinophilia of 9 per cent in 2 chlo- 
rotic' girls. Phosphorus poisoning is also said to cause eosino- 
philia, and Taylor refers to nuclein and pilocarpine as possessed of 
similar properties. 

8. 2I(/elo<jenous Len'ka^mia (see below, p. 168). 

■ 9. Eosino[jhHia in Hcematoma, Hemorrhagic Exudations, and 
Purpura. — Klein {CentrcdhJ. f. inn. Med., January 28th, 1899) re- 
ports two cases of hemorrhagic pleural exudation with a very large 
number of eosinophiles (74 to 76 per cent) in the exudate and a 
marked increase of circulating eosinophiles : 



Case. 


Date. 


Red cells. 


White 
cells. 


Per cent 
htemo- 
globin. 


Per cent 

poly- 
nuclears. 


Per cent 
eosin- 
ophiles. 


Per cent 
lympho- 
cytes. 


1 


^rarch 29 
April 4 
April 11 

(1893) 
April 9 
April 21 

(1894) 


3,800,000 


11.800 
6.200 
8,150 


45 


71.7 
56.5 
44. 

€9.1 
65.1 


12.5 
37.5 
40. 

6.5 
16.1 


15.8 
6. 
16. 

24.3 
18.7 


3 






9,189 



Perhaps of a similar type is the eosinophilia exemplified in the 
following report from a case of simple purpura in a girl of eight. 
White cells, 18,000; eosinophiles, 17.5 per cent; polynuclears, 44 
per cent ; lymphocytes, 39 per cent. 



DlMIXUTIOX IX EOSIXOPHILES. 

1. During digestion and severe muscular exertion. 

2. After castration (Neusser). 

3. In febrile stages of pneumonia, grippe, typhoid, diphtheria, 
sepsis, and most infectious diseases accompanied by leucocytosis. 
That this is not due simply to the presence of fever is shown by 
the fact that in malaria and scarlet fever, despite high fever, eosino- 
philes may be increased. 

4. In the moribund state eosinophiles are diminished or absent. 

5. Malignant disease, hemorrhage, and most of other causes of 
leucocytosis also dimmish the eosinophiles. 



118 



CLINICAL BLOOD EXAMINATION. 



Diagnostic axd Pkogxostic Value of Eosixophilia. 

In triehiniasis eosinophilia is of great diagnostic value. 
Neiisser lias suggested the following points : ' 

1. In the diagnosis between puerperal mania and puerperal 
sepsis, eosinophilia points to the foriner. 

2. Between a tumor connected Avith the giniital S3-stem and one 
not so connected, eosinophilia points to the former. 

3. In determining whether a given case of hysteria, neurosis, or 
psychosis is likely to be benelited b}' castration, the presence of 
eosinophilia favors the operation. 

4. In malignant disease an eosinophilia points to a metastasis 
in the osseous sj^stem (tumors of the spleen are not included in this 
rule). 

5. In cases of doubtful, syphilis eosinophilia combined Avith 
lymphocytosis (see above) speaks in favor of syphilis. 

6. The diagnosis of any obscure form of " uric-acid diathesis " is 
helped by finding an increase of eosinophiles. 

7. In distinguishing malignant liver disease from other liver 
disease eosinophilia points to the latter. 

1. In the pro(/nosU of chlorosis, eosinophilia is favorable. 

2. Ill the prognosis of scarlet fever and scarlatinal nephritis the 
greater the eosinophilia the better tlie prognosis. 

3. After hemorrhage increased eosinophiles show active regener- 
ation of blood and good prognosis. 

4. In pernicious anaemia eosinophilia is favorable for the same 
reason. 

MYELOCYTES. 

The occurrence of the myelocyte of Ehrlich in tlie circulating 
blood is almost always to be looked upon as pathological, that is, 
as the intrusion of a variety of leucocyte naturally a stranger to the 
circulating blood and a permanent inhabitant of the marrow. 
Among hundreds of specimens from healthy persons I have seen 
but one typical m^^elocyte. 

1. The largest number of circulating myelocytes occurs in mye- 
logenous leukaemia (see page IGl ). 

2. In all conditions associated witli stimulation (^f the bone mar- 
row — that is, in all diseases accompanied by well-marked leucocy- 

• For Done of ^vhich I can vouch. 



MYELOCYTES. 



119 



tosis or by severe anaemia of any type, myelocytes in small numbers 
may frequently be found. Thus I have found them in most cases 
of pernicious ansemia and of malignant disease with leucocytosis. 
Tlirck finds them in most acute infections, even in typhoid with 
subnormal leucocyte count. Engel has noted their frequent pres- 
ence in diphtheria, while Neusser* has noted them in various toxic 
conditions such as puerperal mania, osteomalacia, ursemia, carbonic- 
acid poisoning, Basedow's disease, diabetic coma. Others have 
recorded their occurrence in rickets, syphilis, phthisis, general 
paralysis, etc. 

The common elements in these various diseases are ansemia and 
leucocytosis. Accordingly it seems to me reasonable to class them 
as signifying a marrow stimulation, and as much akin to Tlirck' s 
"stimulation forms" (see above, pages 110 and 111). 

The most curious example of their occurrence known to me is 
the following: 

Mrs. W had been starving herself more or less for six 

months from motives of economy. Two weeks before 1 first saw 
her she began to suffer with cystitis. From both these troubles 
she made a rapid recovery, which has persisted now eighteen 
months. There was at the first count a leucocytosis of 15,100; 
partly due to cyanosis, as she had just been having a chill. The 
red cells were 7,300,000. Haemoglobin, eighty-seven per cent. 
Differential counts were as follows : 



Date. 

Number of cells counted. 


May 2d 
800. 
Per cent. 


May 6th 
1,000. 
Per cent. 


May 7th 
400. 
Per cent. 


May 8th 
400. 
Per cent. 


May 13th 

1,000. 
Per cent. 


" Polynuclear neutrophiles". . . 


82.7 


82.2 


83.6 


80.2 


68.5 




8.6 


12.5 


9.4 


11.3 


25.2 




8.2 


1.5 


2.0 


6.0 


5.2 




.5 


3.5 


4.0 


2.5 


.6 




.0 


.3 


1.0 


.0 


.5 



In a general way their presence seems to have about the same 
significance as that of normoblasts, but they occur much more fre- 
quently. As a rule I think they indicate an acceleration of the 
marrow functions by which red corpuscles and granular leucocytes 
are furnished to the blood. Such an acceleration may be supposed 
to take place in leucocytosis, leukaemia, and severe anaemia, which 
are the chief conditions in which myelocytes appear in the blood. 

* Cited in Klein: Volkmann's "Samml. khn. Vortritge," December, 1893. 



CHAPTER IX. 



GENERAL PATHOLOGY OF THE BLOOD AS REGARDS HEMO- 
GLOBIN, FIBRIN, LIPEMIA, MELANEMIA, AND 
HEMORRHAGE. 

HAEMOGLOBIN. 

As stated above, the hsemoglobin may increase and diminish, in 
lines parallel to those of the red cells. In that case we suppose the 
amount of haemoglobin per corpuscle to be normal and the color in- 
dex or valeur glohulaire is said to = 1. When the hsemoglobin is 
diminished more than the count of corpuscles, we say that the color 
index is less than 1. For example, if a man has 5,000,000 red cells 
per cubic millimetre and only 50 per cent of haemoglobin, we esti- 
mate the color index by simply reducing the count of cells to a 
stated percentage (5,000,000 cells = 100 per cent of cells) and 
dividing this percentage into the haemoglobin percentage — i.e., 
= 0.5 = the color index. Therefore 4,000,000 red cells {= 80 per 
cent) with 60 per cent of haemoglobin give a color index of = 0. 75. ' 

The color index rarely goes above 1, except in pernicious anaemia 
(see below). Here it may be as high as 1. 7. As a rule when the red 
cells are above the normal the haemoglobin rises equally, sometimes 
it lags behind a little, but rarely if ever does it rise higher than the 
cells. 

In most anaemias, as has been pointed out, the haemoglobin suf- 
fers markedly before any considerable loss of red cells takes place. 
In other words, the corpuscles seem to get thin before they die, and 
except in malaria, hemorrhage, and a few other cases they are not 
destroyed while in the full vigor of health.' 

The loss of haemoglobin is loss of albumin, the chief constituent 
of the cells, and hence is usually loss of weight. 

In general the changes in the haemoglobin are best studied in con- 

^ This is of course not hteral. There is no reason to suppose that good- 
sized corpuscles get smaller. It is more likely that a smaller generation is 
sent out by the blood-making organs. 



FIBRIN. 



121 



nectioii Avith changes in the count of red cells, and so far as they 
have not already been mentioned will come in under the various 
special diseases. 

Fibrin. 

The fibrin network to be seen in normal blood during coagulation 
(see page 54) is increased in a considerable number of conditions. 
Hayem has studied these minutely, and described several varieties 
of arrangement of fibrin fibres as characteristic of special diseases, 
that is, he studied fibrin qualitatively as well as quantitatively, and 
also as regards the rapidity of its formation. 

The rate of fibrin formation is often not the same as the rate of 
coagulation. It is not parallel to the number of leucocytes or blood 
plates, at least not in all cases (malignant diseases, scurvy). 

In a general way we expect increased fibrin in infectious and 
inflammatory diseases, but there are notable exceptions to this. 
The greater the exudation and the freer it is (in a cavity or on the 
surface) the thicker the fibrin network, while so-called interstitial 
inflammations or such conditions as parenchymatous nephritis show 
little increase in fibrin. The seat of the lesions has no considerable 
influence, except as it modifies the nature of the lesion. An abscess 
in one place has the same effect as an abscess elsewhere, provided it 
is equally free or equally confined, and of the same contents. 

Tuberculosis does not increase fibrin if uncomplicated. Leuco- 
cytosis and fibrin behave alike in many respects, especially in rela- 
tion to the vigor of resistance which the individual opposes to a 
given infection. When the individual is so weakened that he does 
not react well against the infection, the leucocytes and fibrin are 
but slightly increased, whereas in a vigorous individual the same 
infection would have markedly increased both fibrin and leucoc3rtes. 
But neoplasms raise the count of leucocytes without changing the 
amount of fibrin. 

In a general way fibrin increases and decreases as fever does, 
but often persists after fever is gone. 

The most marked fibrin networks are seen in pneumonia, acute 
articular rheumatism, suppurative diseases, and in scurvy. In 
erysipelas it follows the leucocytes (increased in severe, not in mild 
cases). In the early days of grippe it is increased. 

The fever of hysteria or chlorosis shows no increase of fibrin, and 
post-hemorrhagic anaemia with or without fever shows none. 



122 



CLINICAL BLOOD EXAMINATION. 



Fibrin is diiuiiiivsluHl in ])eniicious anaemia^ not increased in leu- 
kieiuiaj typhoid, malaria, ,nialignant disease, non-suppurative dis- 
eases of liver, nephritis (except interstitial ne])hritis, in whicli it may 
he increased), heart disease, pnrpura, haemoglobin uria (sometimes 
decreased). 

The most valuable point about the fibrin appears to be the ab- 
sence of any increase in malignant disease, whereby a diagnosis be- 
tween the affection and a suppuration may be helped. Otherwise 
the information given hy it is chiefly confirmatory of impressions 
given by other features in blood examination. 

Lip.^:mia. 

The blood invariably contains small quantities of fat, especially 
during digestion (v. Jaksch 

In the blood of persons suffering from a variety of diseases such 
as phthisis, diabetes mellitus, obesity, alcoholism, nephritis, and in 
some dyspnoeic conditions, suppressed menses, pregnancy, icterus, 
typhus, malaria, mental disease, diseases of the heart and pancreas, 
as Avell as in health, fat is occasionally to be seen in considerable 
quantities. Grawitz' iiiuls that if the blood is collected in a fine 
capillary tube and this is kept in a horizontal position for some 
time, fat rises to the surface like cream, and can be seen with an 
oil-immersion lens in the form of fine drops. Gumprecht ^ demon- 
strated it with osmic acid, which stains the fat drops black, and 
proved them to be fat by dissolving them in ether, xylol, etc. 

Lipa^juia has no special significance so far as is known, and is 
not characteristic of the diseases above mentioned. Its cause is 
unknown. 

[In almost any preparation of the fresh blood fat drops are to 
be seen unless the patient's skin is washed with alcohol before 
puncturing. Even with thes(^ ]n'ecautions a few drops may often 
be seen in healthy people's blood.] 

Melax-emia. 

In malaria the occurrence of a black pigment in the leucocytes 
which have taken plasmodia into themselves, is generally to be seen 
during and shortly after a ])aroxysni. Piginent free in the blood 
is to be seen only at the moment of segmentation among the new 

1 "Klin. Diagnostik," p. 75 (English translation). 
^Loc. cit., p. 160. ^ ^T>eut. med. Woch., 1894, No. 39. 



BLOOD REGENERATION. 



123 



generation of jDarasites. The same condition has been observed in 
relapsing fever and in persons suffering from melanotic malignant 
tumors, the pigment being always in the white corpuscles. Pre- 
sumably it must at some time be free in the plasma, but it is rarely 
if ever seen outside the cells. 

In Addison's disease Tschirkoff' ' observed pigment in the leuco- 
cytes. 

Hemokrhage. 

Women can stand a greater hemorrhage than men. Children, 
on the other hand, succumb to comparatively slight hemorrhages 
{cf. Blood in Infancy, page 445). Individual differences make a 
great difference in the ability to survive hemorrhage, and no exact 
amount of blood can be stated as the maximum that any one can 
lose and yet survive. 

CJianges in the Blood Resulting from Hemorrhage. . 

The red cells and haemoglobin of course suffer proportionally at 
first; later the haemoglobin in the newly formed cells is always 
deficient (see below). 

The striking point in the blood after hemorrhage is the evidence 
it gives us that even before the hemorrhage has ceased the other 
tissues begin to contribute fluid to make up the volume upon which 
life depends. The serum is markedly diluted by this fluid, but still 
serves to give the heart something to contract on and so prevents 
blood pressure from falling as fast as it otherwise would do. Were 
it not for such contributions from neighboring tissues the organism 
could sustain but slight hemorrhage without succumbing at once. 
We have then after hemorrhage a diluted or hydraemic blood, even 
though we do not assist the efforts of nature by contributing fluid 
by intravenous or rectal injection. Behier reports a case due to 
trauma in which the count was only 688,000 pe* cubic millimetre. 

Coagulation increases in rapidity the more blood is lost, so that 
after severe hemorrhage it takes place almost instantly. 

Blood Eegeneration. 

The regeneration of the blood after hemorrhage may be taken as 
typical of the same process in anaemia from other causes. 

iZeit. 1 kliii. Med., vol. xix., 1891. 



124 



CLINICAL BLOOD EXAMINATION. 



Tlie length of time needed for full restoration to normal depends 
not merely on the (a) amount of blood lost, but also on the {b) age 
and nutrition of the patient as well as upon (c) the methods of treat- 
ment carried out and the existence of (cT) other disease (tyj)lioid, 
malignant disease, phthisis, etc.). 

Allowing for these other conditions we may say that, other 
things being favorable, the loss of 

I. Less than 1 per cent of the blood mass is made up in 2 to 5 days. 
II. From 1 to 3 " " " " " 5 14 

III. " 3 " 4 " " " " " 14 " 30 " 

The last amount means a very severe hemorrhage. Few surgical 
operations involve the loss of over three per cent, and after such ac- 
cordmgly we expect the blood to be normal again in two weeks, pro- 
vided the individual is otherwise sound (see Malignant Disease, page 
373). 

Young, well-nourished persons are of course quicker in making 
up losses than the old and weak. 

Blood Condition During Regeneration. 

1. Red Cells. — (A) As previously mentioned, the haemoglobin 
becomes relatively low as soon as the regenerative process is well 
established, and as recovery progresses the red cells are almost al- 
ways normal in numbers for some time before the stature, weight, 
and color of the individual cells is what it should be. A color in- 
dex of 0.50-0.60 is not unusual — in short, what some call a ''chlo- 
rotic " condition of the blood. 

(B) Qualitative changes are those already described on page 83, 
namely: («) Deformities in size and shape with an average diminu- 
tion in size ; (h) polychromatophilic cells ; and (f ) nucleated 
corpuscles. These latter are almost exclusively of the normoblast 
type, but an occasional megaloblast has been observed. 

Blood Crisis. — Yon Xoorden was the first to notice that in some 
cases nucleated corpuscles are to be found in the circulation in great 
numbers for a few hours onh^, the blood examination both before 
and after showing few or none at all. The name of " blood crisis 
has been given to these sudden outpourings of nucleated red cells ; 
they are to be observed during recovery from various forms of 
anaemia. 



BLOOD REGENERATION. 



125 



2. White Cells. — Immediately after a loss of blood we can 
usually find a decided leucocytosis despite the dilution of the blood 
(see above, Post-hemorrhagic Leucocytosis). 

This leucocytosis is in no way different from those occurring 
from other causes. The percentage of polymorphonuclear cells is 
usually increased, and the eosinophiles often disappear. As pointed 
out by Stengel we may have a lymphocytosis after hemorrhage, 
either from the start or following a polynuclear leucocytosis. In 
his case the percentages were: Polynuclears, 43.5; lymphocytes, 
43.5; transitionals, 10; eosinophiles, 2.8. A case of anaemia from 
bleeding piles, in which the red cells were 2,723,000 and the haemo- 
globin 35 per cent, showed in a total leucocyte count of 4,200, 69 
per cent of small lymphocytes and only 28 per cent of polymorpho- 
nuclear cells. Leucocytosis if present is rarely very high, seldom 
reaching over 30,000. It is not invariably present, or if present 
sometimes is of very short duration. Thus in a patient whose red 
cells were reduced to 3,200,000 by a prof use uterine hemorrhage the 
white cells counted next day were only 8,000; while in the next 
bed of the hospital was a woman crushed in a railroad accident 
whose red cells were 1,280,000, and the white cells 28,000, the 
usual state of things. 

The leucocytes may be increased even by a eerehral hemor- 
rhage which is not large enough considerably to affect the red 
cells in most cases. Ten apoplectic cases (with autopsy) ob- 
served at the Massachusetts Grenerai Hospital showed such counts 
as the following : 

1. Red cells 5,512,000, white cells 25,000, Hb. 85 per cent. 

2. Red cells 5,560,000, white cells 15,600, Hb. 90 per cent. 
Whether the leucocytes are here affected by any influence other 

than that of hemorrhage I do not know. 

The effect of transfusion (intravenous saline solution) is appar- 
ently at first to increase the leucocytosis. 

D , a patient with traumatic rupture of the urethra, had had 

severe hemorrhage for forty-eight hours before it was checked at 1 
P.M., November 1st, 1895. At 4 p.m., his pulse being 165, the 
count showed red cells, 3,304,000; white cells, 10,400. He was 
at once given a pint of sterilized normal salt solution by intra- 
venous injection under the strictest asepsis. Ten minutes after 
the transfusion the leucocytes numbered 32,400. One hour later, 
they were 24,700, and the red cells 3,632,000. Four hours later, 



126 CLINICAL BLOOD EXAMINATION. 

leucocytes, 31,900; red cells, 3,046,000. The later counts were 
as follows.- 

Red t ells. White Cells. 

November 2d: good pulse 3.608.000 34,600 

2d (o P.M.): good pulse 2,944,000 30.200 

3d (4 P.M.): good pulse 2.928.000 15.800 

13tli 3.360.000 16,600 

A good recovery was made. 



Impoetaxce for Surgery of Blood Counting After 
Hemorrhage. 

Mikulicz, who as a surgeon, should speak with authority and 
who always takes account of the condition of the blood in his cases, 
lays down (following Laker) the following rule : Xever operate on 
any ease when flie luvnKXjhihln is helo/r fJi irfi/ ppy rent. The question 
of operating at once or waiting for recovery from " slioek/" is a very 
common one in the accident rooms of any hospital and is generally 
settled on general impressions of the patient's vigor. We know, 
say, that he has lost blood, but we have no way of ascertaining how 
much. If his shock " is due to hemorrhage he may need transfu- 
sion ; if it is due to cerebral concussion or compression, the trans- 
fusion will do more harm than good. The blood count can settle 
these questions, and could reveal much which is now obscure, if it 
Avere more frequently employed in surgical cases and a standard like 
that of Mikulicz worked out. 

In cases of suspected ruptured tube in extra-uterine pregnancy, 
the question of whether the patient is suffering from mternal con- 
cealed hemorrhage can be settled in many cases by the blood count, 
which will show a decided loss of red cells if the hemorrhage is 
large, and thereby distinguish the condition from peritonitis, ob- 
struction, or strangulated hernia, none of which affects the red cells. 
Any other concealed hemorrhage, as for instance from ruptured kid- 
ney or spleen or liver, maybe indicated by the blood count when by 
other physical signs the diagnosis might be ver}' difhcult. 

Su innmrif. 

The blood count is of importance after cases of supposed hemor- 
rhage. 

1. To ascertain whether such has taken place. 

2. Its extent. 



CHRONIC HEMORRHAGE. 



127 



3. Whether operation is to be immediate or not. 

4. Whether transfusion is indicated. 

5. How soon the patient has got back enough blood to make 
operation worth while. 

Chroxic Hemorrhage. 

Piles, uterine disease, haemophilia, purpura, and other causes 
may produce a long-standing drain on the blood. 

Some patients apparently can lose a little blood almost daily for 
years without acquiring any severe anaemia, and if the individual 
is otherwise sound and does not suffer from an underlying disease 
like phthisis, cancer, or nephritis, he can probably go on for a long 
time without showing any bad effects from the repeated small hem- 
orrhages. How much he can stand we have no way of judging, for 
we cannot measure the amount of blood lost. When, however, such 
small repeated losses do produce an anaemia, regeneration is apt to 
be much slower than after a single large hemorrhage. The longer 
the drain has been going on the poorer the chance for recovery, and 
the slower the latter will be if it does take place. 

Grain in body weight does not always mean gain in corpuscle 
substance as well (see Malignant Disease, page 373). 



BOOK IL 

SPECIAL PATHOLOGY OF THE BLOOD. 



9 



PART I. 



CHAPTER I. 

THE PRIMARY ANEMIAS. 
1. THE BLOOD IN PERNICIOUS ANEMIA. 

1. Volume and Oxygen Capaeitij. — J. Lorrain Smith, studying 
the blood of seven cases by the carbonic-oxide method, concludes 
that "absolute loss of oxygen capacity (= haemoglobin), which in 
chlorosis practically does not occur, is here of primary importance. 
Whereas, in chlorosis, the oxygen capacity is 95 per cent of the 
normal, here it averages 48 per cent, and in one case was but 28 per 
cent." 

The volume of blood is sometimes markedly increased, sometimes 
normal, sometimes diminished. Patients with a large volume of 
blood seem to feel worse than those with normal volume, even when 
the haemoglobin percentage and count of corpuscles are approximately 
the same. In the remissions of the disease the volume may be rapidly 
reduced. So, for example, 4,305 c.c. with 1,100,000 red cells per 
cubic millimetre and later (in remission) 2,775 c.c. with 3,104,000 
red cells per cubic millimetre. 

2. Gross A2Jpea7'anGes. 

(a) The drop as it emerges from the puncture is often exces- 
sively pale and watery, but not more so than may occasionally be 
seen in secondary anaemia or chlorosis. Sometimes it is not nearly 
so pale as in other cases with equally low counts, a fact which may 
be due to the increased color index sometimes present (see below). 

In several early cases I have seen the blood as red as normal. 

Another appearance, which I have frequently observed in this 
and other anaemias, is an uneven, streaked color in the drop, as if 
the cells were unequally divided in the jolasma. 

(b) As striking as the color of the drop is its great fluidity ; the 
rapidity with which it slips off the ear or finger often makes it diffi- 



132 



SPECIAL PATHOLOGY OF THE BLOOD. 



cult to suck it up in time. It is usually very slow in coagulating. 
When drawn the blood does not separate into serum and clot, even 
after the lapse of seventy-two hours (Lenoble) . 

(c) The fresh specimen in most cases shows no rouleaux forma- 
tion, and a marked diminution in blood plates and fibrin. Hayem 
says : " This double lesion, rarity of blood plates and loss of retrac- 
tility on the part of the clot, is, according to my latest observations 
(1900) , the most characteristic sign of this form of primary ansemia. " 
I have no experience on this point. 

There are usually great variations in the size and shape of the 
corpuscles with a tendency to an oval shape and an increase in the 
average diameter. Not infrequently the deformed corpuscle shows 
active pseudo-amoeboid motions of its projecting points or of the 
cell as a whole. The great lack both of red and white cells is 
noticeable even in the fresh specimen. 

Red Cells and Hcemoglohin. 

(a) Quantitative changes (see Table I.). The average count of 
red cells in the one hundred and ten cases of my table is about 
1,200,000, which may be taken as the average count in patients 
seen at the stage of the disease at which they feel sick enough to 
seek medical advice.' We very rarely get an opportunity to ex- 
amine the blood in the early stages of the disease, so that we have 
to judge of them chiefly from the evidence given during the remis- 
sion so commonly observed. In the relapse following such a remis- 
sion the blood count may fall from 5,000,000 to 1,000,000 in a 
period of from six weeks to six months. In the later stages of the 
disease 500,000 red cells per cubic millimetre is not rare, and if the 
diminution has been gradual, the patient may be up and about and 
able to do light work with a count no greater than this. I had an 
opportunity to observe such a case in the wards of Dr. F. C. Shat- 
tuck at the Massachusetts General Hospital five years ago, in which 
for several weeks the blood count remained at or near 500,000, yet 
the patient was outdoors daily, read the papers, and seemed per- 
fectly comfortable. Evidently it is not the anaemia itself which 
kills the patient. 

The lowest count on record is that reported by Quincke — 143,000 
per cubic millimetre. This case later improved so much that the 

' Cf. Schaumann: Out of his 88 cases, 1 was over 3,000,000; 26 were be- 
tween 1,000,000 and 2,000.000: It below 1,000,000; average 1,290,000. 



THE PRIMARY AN^.MIAS. 



133 



corpuscles rose to 1,234,000 within seventy-four clays of the count 
of 143,000. She lived several months "fat and well nourished." 

Table I. 



Pernicious Anaemia^ (110 cases). 
The red cells ranged : 

From 500, 000 to 1 , 000, 000 in 27 

" 1,000,000 to 1,500,000 in ... 45 

•* " 1,500,000 to 2.000,000 in 34 

Total cases under 2,000,000 106 

From 2, 000, 000 to 2, 500, 000 in 4 

110 

b. Leucocytes numbered : 

Under 1,000 9 

1,000 to 8, 000 23 

3,000 to 5,000 40 

5,000 to 7, 000 24 

7,000 to 10,000 12 

10,000 to 13,000 2 

110 

c. Haemoglobin: 

Relatively liigh in 79 

Not relatively high in 31 

110 

d. Average diameter of red cells at time of final examination : 

Increased in 89 

Not increased in 21 

110 

e. Megaloblasts at time of first examination : 

Predominated in 87 

Later examination, predominated in 20 

Only one examination, no megaloblasts 3 

. 110 

/. Lymphocytes between 20 per cent and 30 per cent in 84 

30 " "40 " 84 

40 " "60 " 33 

60 " "80 " 6 

80 " "90 " 3 



110 

* For complete records of these cases see Appendix B. 



134 ^ SPECIAL PATHOLOGY OF THE BLOOD. 



g. Eosinophiles : 

Under 4 per cent 90 

Over 4 percent , 13 

None found 7 

110 

7^ Myelocj'tes. Present in 66 cases. Highest percentages: 

10 per cent in 2 

9 " " 1 

8 " " 2 

_ ^, 0 



7 

The great but temporary improvements above alluded to, fol- 
lowed by relapse, occur either with, or without treatment. In the 
course of a few months the count of red cells may rise to normal, 
the nucleated corpuscles (see below) disappear, and the patient is 



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THE PRIMARY ANAEMIAS. 



135 



apparently restored to health and goes to work with a langh at the 
doctor. I have followed one case through five such relapses in a 
period of three years before the fatal issue came. Frequently the 
patient feels so well during one of these remissions that he goes to 
work and is lost sight of, and, under such conditions, the incautious 
are apt to report "cure." 

The acGom'panyiiig cliarfs^ show the three types usually met 
with ; No. II. being, of course, only a fragment of a case similar to 
No. I., while the steady progression of No. III. may have been 
preceded by a rise from a former downfall, though no such history 
was obtained. 

Looking over a considerable number of cases, one can hardly 
help being struck with the tendency of the count to remain near the 
figure 1,000,000. The red cells rarely remain stationary at, say, 
2,000,000, and often death may occur without the red cells sinking 
below 1,000,000. It seems as if some self-applying mechanism 
tended to arrest the destruction of corpuscles at or near this point. 

In counting the red cells some difiiculty and error may result 
from the very small size of some of the cells. It is especially im- 
portant that the diluting solution should be clean and freshly mads, 
else without the aid of a stain it may be hard to distinguish the 
dwarf cells or microcytes from bits of extraneous substance. 

Quantitative Changes. 

White Corpuscles (see Table I.).— The rule is a very consider- 
able diminution in the number of leucocytes. Thus of 110 cases 
which I have examined 71 were under 5,000, the average of all 
being 3,800. 

[I have excluded from this series counts made immediately after 
hemorrhages and counts in infants. The latter are very apt to show 
a leucocytosis in connection with any form of anaemia.] 

As the disease progresses the leucocytes fall even more rapidly 
than the red cells, and counts as low as 500 white cells per cubic 
millimetre are not uncommon. 

Leucocytosis when present in the blood of adult cases is always 
due to some complication like hemorrhage or suppuration. 

As mentioned above, the blood plates and fibrin are much di- 
minished. 

^ The number of perpendicular Hnes represents the number of weeks. 



136 SPECIAL PATHOLOGY OF THE BLOOD. 

Table II. — White Cells. — First Examination in Sixty Cases. 



1 

2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 



White cells. 



400 
500 
800 
1,000 
1,000 
1,000 
1,500 
1,600 
1.800 
2,000 
2,000 
2,000 
2,000 
2,000 
2,300 
2,600 
2,800 
2,800 
2,800 
2,800 



21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
84 
35 
36 
37 
38 
39 
40 



White cells. 



2,900 
3,000 
3,000 
3,200 
3,200 
3,300 
3,400 
3,500 
3,600 
3,700 
3,704 
4, 000 
4,000 
4,000 
4,000 
4,200 
4,300 
4,400 
4, 500 
4,720 



41 
42 
43 
44 
45 
46 
47 
48 
49 
50 
51 
52 
53 
54 
55 
56 
57 
58 
59 
60 



White cells. 



4,828 
4, 900 
5,000 
5, 200 
5,300 
5,500 
5,600 
6, 000 
6,000 
6,000 
6,400 
6,500 
7,000 
7,200 
7, 500 
7,600 
9,000 
9,600 
10,000 
10,100 
=: 3, 800 + 



In four eases in which Dr. Lindstrom, of Boston, was kind 
enough to give massage, we were unable to see the slightest gain 
either in corpuscles or haemoglobin, such as can be produced tem- 
porarily in most healthy persons. The observations of J. Mitchell 
on this point we Avere unable to confirm. 

Hcemoglohin. 

The great majority of cases of pernicious anaemia have a rela- 
tively high percentage of haemoglobin {e.g., 1,000,000 red cells and 
35 per cent of haemoglobin, or a color index of 1.75). Ehrlich has 
several times found it over 50 per cent even in the severest cases, 
and once as high as 65 per cent. 

This high color index is not, however, peculiar to this disease. 
The same condition has been noted in acute leukaemia, in " splenic 
anaemia " (McCrae), and in leprosy. 

Of the 110 cases in the series on page 133, in which the haemo- 
globin was tested, a color index of over 1 was apparently present in 
79, or 71 per cent, and a color index of less than 1 in 31, or 29 per 
cent, of the cases. How many of these haemoglobin estimations 
may have been wrong I cannot say. 

From the frequency with which we lind the corpuscles well 
stained and larger than normal in pernicious anaemia (see below), we 



THE PRIMARY ANJ2MIAS. 



137 



should expect that the hsemogiobin would be relatively high, and in a 
larger percentage of cases than the v. Eleischl instrument indicated. 

An increased color index is probably a bad prognostic sign. In 
the remissions of the disease when the cells are increasing fast, the 
haemoglobin lags behind and the color index is low. As the relapse 
follows, the color index in many cases progressively increases. 
Cases ivhose color index is low and in which the average diameter of 
the red cells is normal are apt to be gaining at that time, while those 
with high color index are apt to be losing at that time. 

The average color index in the cases in which the hsemoglobin 
and red cells were both tested was 1.04, the average percentage of 
haemoglobin being 26 and of corpuscles 24 (= 1,200,000). 

Qualitative Chaxges. 
1. Red Corpuscles. 

We must distinguish here between 

I. The active stages of the disease and 

II. The remissions. 

In the active stages we find : 

(a) Increase in the average diameter of the cells is a very con- 
stant and striking feature of the stained specimens in this disease. 
In no other disease do so large cells or so many of them occur. 

The average diameter may rise as high as 11 to 13 p., but as a 
rule the average is reduced by the presence of a few abnormally 
small forms. The percentage of oversized cells gives us a better 
idea of the facts. Thus Ehrlich in 8 cases of pernicious anaemia 
found the following percentages of oversized red cells : 71, 71, 66, 
65, 60, 58, 57, 56. 

Out of one hundred and ten cases in which I have looked for this 
point, eighty-nine showed the increase, as far as could be judged 
without measuring any large number of cells. This does not mean 
that every cell is larger than normal, but that those larger than 
normal outnumber those undersized ; the " macrocytes " are more 
numerous than the "microcytes." Occasionally we see cells over 
20 ,a in diameter, some with nuclei, some without. 

{b) Deformities in Sha^je. — The eye soon gets used to the shapes 
assumed by the necrobiotic corpuscles and learns to distinguish them 
from the distortions due to technique or to crenation. Most of them 
fall under one or another of the types shown in Plate IV. The very 



138 



SPECIAL PATHOLOGY OF THE BLOOD. 



large forms are generally oval, but seldom present any further de- 
formities. Among the smaller cells the battledore and sausage- 
shaped forms are very common. In one case I found all the red 
cells of the latter shape, so that they looked at first sight like a lot 
of gigantic bacilli. That this appearance was not due to the tech- 
nique^ (as I had at first supposed) is probable from the fact that the 
rod-shaped cells did not point all in one direction as they would 
have done if pulled out of shape by the process of spreading (see 
Fig. 29) . This appearance is only an exaggeration of what may be 




Fig. 39.— Elongated or Oval Corpuscles in Pernicious Anaemia. 



seen in most severe ansemias, namely, a tendency toward an oval 
shape like that of amphibian corpuscles. This is usually true of 
those cells (in pernicious cases) which are not more violently de- 
formed. The type of cell so common in secondary anaemia — well 
stained at the edges and pale in the middle (Litten's "pessary 
forms ") are rarely seen. 

Occasionally we see cases with no considerable deformities what- 
ever in the red cells. In nine cases out of sixty in which this point 
was observed, little or no deformity was noted. I cannot make out 

^ Some writers advise the use of less heat than usual in dealing with cover- 
glass specimens of pernicious ancemia. I have not found this so, and heat as 
usual up to 150° C. and then stop. 



THE PRIMARY ANEMIAS. 



139 



that such cases have any better or worse prognosis than others. I 
have never seen cases whose red cells were all undersized, but a 
normal average diameter was present in somewhat under one-quar- 
ter of the cases in which I have looked out for this point. 

(c) Stain uig Froperties of the Red Cells. — The white spots or 
streaks described by Maragliano, Hayem, and others are very often 
seen in the red cells of pernicious anaemia despite good technique. 
Some corpuscles are so pale in the centre that we see only the 
narrow ring of stained protoplasm at the periphery, a mere shell. 
Others are swollen up so as to show no sign of central biconcavity, 
and stain deeply and evenly all over. 

More common than in any other form of anaemia are the polychro- 
matophilic red cells (see Plate IV.) which with the Ehrlich-Biondi 
mixture stain brownish, purple, or gray, either as a whole or in parts. 
In cover-slips stained with thionin the spotted appearance of the pro- 
toplasm described by Ehrlich and G-rawitz is usually marked. In the 
nucleated red cells the protoplasm is very apt to show these changes. 
In some cases it is difficult to distinguish normoblasts from lympho- 
cytes. In difficult cases we have sometimes to fall back upon the ap- 
pearances of the periphery, which in most red corpuscles shows 
some thin place or crinkle characteristic of 2iflat cell, while the lym- 
phocyte gives us the more solid-looking outline of the spherical cell. 

All these microchemical changes can be better brought out with 
hsematoxylon-eosin or eosin-methyl-blue stains, but all that is 
needed for clinical purposes can be made out with the ordinary 
Ehrlich-Biondi mixture. 

2. Nucleated Bed Corpuscles. 

Nothing further needs to be said in description of these forms 
(see above, pages 89-93). We have no exact method of estimating 
the number of nucleated cells either in relation to the whole number 
of red cells or in a cubic millimetre. All we can do is to note the 
number seen \i\ sucJt an area of a cover-glass specimen as is covered 
while counting a given number of white cells, say 1,000. Knowing 
the ratio of red to white corpuscles, we can calculate from this 
number of nucleated red cells their approximate relation to the 
whole number of red cells. 

Thus if the ratio of white to red be 1 : 1,000 (1,000,000 red and 
1,000 white) and we have seen two nucleated red corpuscles while 
making a differential count of 1,000 white cells, the total number 
of red cells passed over must be approximately 1,000,000 and the 



140 



SPECIAL PATHOLOGY OF THE BLOOD. 



number of nucleated corpuscles about 2 : 1,000,000 red cells or 
two in a cubic millimetre. Of course when leucocytosis is present 
and the ratio is raised — say to 1: 150 (10,000 white and 1,500,000 
red) — finding two nucleated red cells while counting 1,000 white 
would mean that there were two nucleated cells in every 150,000 
non-nucleated, or twenty in a cubic millimetre (or in 1,500,000 
non-nucleated cells). 

Such calculations are inaccurate because we are never sure that 
the red cells and Avhite cells are distributed in the dried specimen 
exactly as they are in the blood. Part of the leucocytes may be 
accumulated at the edges of the cover-glass so that the ratio in the 
middle may be different from that in the circulating blood. 

Nevertheless we can get some idea of how plentiful the nucleated 
corpuscles are, and as their significance in prognosis depends far 
more on their kind than on their numher, greater accuracy as to the 
latter is not at present important. For instance, two megaloblasts 
per cubic millimetre mean a worse prognosis than twenty normo- 
blasts, provided there are no other kinds present in either case. It 
is the ratio of megaloblasts to normoblasts and not the absolute 
number of each, that is of importance. 

In all but three of the cases of pernicious anaemia in which I have 
examined the blood, the number of megaloblasts has exceeded the 
number of normoblasts, and as the cases grew worse the megalo- 
blasts grew relatively more numerous (often absolutely as well). 
Further, in several hundred cases of severe secondary anaemia I have 
never yet seen the number of megaloblasts exceed the number of 
normoblasts. 

The range of variation in the number of nucleated cells present 
has extended in my series from 6 per cubic millimetre to 7,100 per 
cubic millimetre (see Table III.). The calculation can be made by 
using the following formula : 

Let n = the number of white cells counted (by differential count). 
" m = " " nucleated red cells seen while counting these. 

" p = " " white cells per cubip millimetre (Thoma-Zeiss). 

m 

p X — = X = number of nucleated red cells per cubic millimetre. 

n 

The search for nucleated corpuscles in pernicious anaemia is 
sometimes the most laborious undertaking in all blood exammation, 
but it is also one of the most important. We may search two or 
three hours before finding one nucleated corpuscle, but on that cor- 
puscle may hang the character of our prognosis. If it be a megalo- 



THE PRIMARY ANJEMIAS. 



141 



blast and no other nucleated red corpuscles are seen, the prognosis 
is bad, and it is important that we should know it. This is partic- 
ularly true when the case is seen during a remission, for under these 
conditions we might never suspect a case of pernicious anaemia but 
for the presence of niegaloblasts. They are not always difficult to 
hnd ; indeed, in one of my cases they were nearly as numerous as 
the white cells, but, as a rule, we do not get off with less than two 
hours' work. 

The number of niegaloblasts in the peripheral circulation often 
varies very markedly from day to day so that to-day it may be al- 
most impossible to hnd any, while to-morrow they will be plentiful. 
Even in different preparations made at the same time the number of 
megaloblasts may vary greatly. The importance of frequent ex- 
aminations is obvious in the light of these facts. 

Table III. shows the number of nucleated corpuscles per cubic 
millimetre in thirty of the cases examined by the writer. 

Tabt.e III. — Number of Nucleated Red Cells pek Cubic Millimetre 
IN Thirty Cases op Pernicious An.*:mta. 



Case Number. 


Total nucleated 
red cells. 


Megaloblasts. 


Normoblasts. 


Microblas 


•1 


7,100 


5,300 


1,325 


475 


2 


6,468 


3,476 


924 


2,068 


3 


854 


574 


266 


14 


4 


277 


277 


0 


0 


5 


240 


160 


80 




6..... 


229 


123 


106 




7 


208 


130 


78 




8 


200 


134 


66 




9 


117 


103 


14 




10 


116 


80 


36 




11 


114 


95 


19 




12 


112 


96 


16 




13 


96 


96 


0 




14 


96 


84 


12 




15 


92 


59 


33 




16 


46 


26 


20 




17 


45 


36 


9 




18 


39 


33 


6 




19 


35 


32 


3 




20 


28 


26 


2 




21 


28 


21 


7 




22 


28 


28 


0 




23 


18 


12 


6 




24 


14 


14 


0 




25 


11 


11 


0 




26 


11 


10 


1 




27 


11 


9 


2 




28 


9 


6 


3 






8 


7 


1 




30 


3 


2 


1 





142 



SPECIAL PATHOLOGY OF THE BLOOD. 



3. White Corpuscles. 

Unless the cover-glasses are spread unusually thickly, it may 
take a long time to find enough leucocytes for an accurate differen- 
tial count, so great is the leucopenia in many cases. It is worth 
while, therefore, to spread some cover-glasses more thickly than 
Avould be advisable if we had only the red cells to examine. Such 
preparations should be dried at once by artificial heat. 



Table IV. — Percentages of Leucocytes in Pernicious Anemia. 



AND Small. 


EOSINOPHILES. 










Number of 








counts. 


Per cent. 


No. 


Per cent. 




79 


1 


9. 


1 
i. 


77. 


2 


6.2 


1 
J 


71. 


3 


6. 


1 

X 


61.6 


4 


4.7 


2 


58. 


5 


4.6 


2 


57. 6 


6 


4.5 


Q 
o 


57. 2 


7 


4.4 


1 

L 


57. 


8 


4.3 


1 
i 


56 9 


9 


4. 


1 


56. 


10 


4. 


5 


53.9 


11 


4. 


1 


53.8 


12 


3.7 


2 


51.5 


13 


3.5 


1 


49.5 


14 


3.4 


2 


49.4 


15 


3.4 


1 


47.9 


16 


3.1 


1 


47.9 


17 


3. 


3 


47. 


18.. 


2.8 


2 


46. 


19 


2.7 


2 


45.9 


20 


2.6 


1 


45.5 


21 


2.6 


3 


44.7 


22 


2.6 


2 


43.7 


23 


2.6 


1 


42.2 


24 


2. 


1 


41. 


25 


2. 


1 


40.8 


26 


2 


2 


40.5 


27 


L6 


1 


39. 


28 


1.6 


1 


38. 


29 


1.5 


5 


38. 


30 


1.5 


2 


37.8 


31 


1.5 


1 


36.1 


32 


1.5 


1 


35.7 


33 


1.4 


1 


35.6 


34 


1.2 


3 


35.6 


35 


1.2 


1 


34. 


36 


1.3 


1 



THE PRIMARY ANEMIAS. 



143 



Table IV.— Percentage op Leucocytes in Pernicious Anemia 
( Continued). 



Lymphocytes, Large and Small. 



No. 



37 
38 
39 
40 
41 
43 
43 
44 
45 
46 
47 
48 
49 
50 
51 
52 



Per cent. 



33.6 

33.1 

33. 

33. 

31.8 



29. 



27. 

27. 

26. 

24.2 

22. 

21.2 

19.8 

16. 



EOSINOPHILES. 



No. 



37 
38 
39 
40 
41 
42 
43 
44 
45 
46 
47 
48 
49 
50 
51 
52 



Per cent. 



Number of 
counts. 



The essential point shown in these tables is the absolute and 
relative diminution in the polynuclear cells which corresponds with 
a percentage increase in the other forms. Absolutely the lympho- 
cytes are about normal. 

In 52 cases examined by myself the lymphocytes (large and 
small) averaged 45.4 per cent. About nine-tenths of these were 
small forms. As the fatal termination approaches, the percentage 
of lymphocytes rises. An extreme case of this change has already 
been recorded on page 103. Two other cases showed respectively 71 
and 79 per cent of lymphocytes a few days before death. The poly- 
morphonuclear cells suffer proportionately as a rule. On the other 
hand, Ewing has observed a marked rise in the percentage of the 
polynuclear cells near death, although autopsy revealed no compli- 
cation. Pneumonia or septic complications may produce an ordi- 
nary polynuclear leucocytosis. 

Eosinoi^hiles are occasionally increased, 9 per cent being present 
in one of my cases, 6.6 per cent in another. The average of 78 
examinations in my 52 cases is 2.7 per cent. 

Small percentages of myelocytes are the rule. They are present 
in 42 of 52 cases. Table V. shows the percentages. 

As has been explained above (page 119), the myelocyte is found 
in a great variety of affections, although very sparingly in most, 



144 



SPECIAL PATHOLOGY OF THE BLOOD. 



1 

2 

3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16, 
17, 
18, 



Percentage 
of myelocytes. 



9.2 

8.8 

8. 

6.3 

6. 

4.6 

4. 

4. 

3.6 

3.4 

3. 

3. 

2.7 

2.5 

2.2 

2.2 

2.2 

2.0 



19 

20 

21 

22 

23 

24 

25 

26 

27, 

28. 

29. 

30. 

31. 

32. 

33. 

34. 

35. 

36. 



Table V. 



.8 
.8 
.8 
.6 
.6 
.6 
.6 



Average 



Percentage 
of myelocytes. 



0.6 
.6 
.5 
.4 
.3 
.2 
.0 
.0 
.0 
.0 
.0 
.0 
.0 
.0 
.0 
.0 

2 per cent. 



No. 



Percentage 
of myelocytes. 

8 
,5 
5 
5 
4 



No. 

37 .. 

38 ... 

39 ... 

40 . . . 

41 . . . 

42 ... 

43 ... 
44... 

45 . . . 

46 ... 

47 ... 

48 ... 

49 ... 

50 . . . 

51 . .. 

52 ... 



but, so far as my observations go, its presence is more constant and 
the percentages run higher in pernicious anaemia than in any other 
disease except leukaemia. -I am speaking now of percentages. 
With a leucopenia such as is usually present in pernicious anaemia, 
2 per cent of myelocytes means absolutely a very small number per 
cubic millimetre. 

Taking 3,800 leucocytes per cubic millimetre as the average for 
pernicious anaemia (see above, page 135), 2 per cent of myelocytes 
amounts to only 76 per cubic millimetre. In leukaemia the absolute 
number of myelocytes is seldom under 150,000 per cubic millimetre. 

The Blood in Iie/ti isslo/is. 

1. The Color Index. When the red corpuscles begin to in- 
crease the color index may remain relatively high or even become 
still higher (Laache, Schaumann) ; but in the majority of cases this 
is not so. As a rule, in the remissions of the disease the haemoglo- 
bin is relatively low, as in ordinary symptomatic anaemia, and I have 
seen two cases which, if examined for the first time during the period 
of. remission, would have certainly been mistaken for ordinary chloro- 
sis. 

2. The Leucocytes. Coinciding with the increase in the red 
cells there is usually a still greater increase in the leucocytes, so 



THE PRIMARY ANAEMIAS. 



145 



that for a time a moderate leucocytosis may ])e present. This in- 
crease is made up very largely of polymorphonuclear neutrophiles, 
and is due, no doubt, to the increased activity of the marrow 
through Avhich both red corpuscles and granular leucocytes are mul- 
tiplied. The eosinophiles may also be increased as in the following 
case of Ehrlich: Red cells, 4,115,000; white cells, 18,300. Differ- 
ential count of 400 cells showed: Polynuclears, 78.2 per cent; 
lymphocytes, 12; large mononuclear, 0; eosinophiles, 9.5 per cent. 
In another similar case he found 11 per cent of eosinophiles. 

As the percentage of polymorphonuclear neutrophiles increases 
the percentage of lymphocytes decreases, and the myelocytes, which 
are usually present in small percentages during the active stages of 
the disease, disappear. The number of megaloblasts steadily de- 
creases, and in their place normoblasts appear for a time; later 
they, too, leave the circulating blood. The size of the individual 
red cells is sometimes greater during a remission of the disease than 
at any other time. In one remarkable case the patient, whose 
symptoms had totally disappeared and who was actively at work as 
a newspaper correspondent, dropped in to see me one day, appar- 
ently in splendid health and sjoirits. His skin and mucous mem- 
branes were ruddy red, his haemoglobin 90 per cent, yet to my 
great surprise I found only 2,500,000 red cells to the cubic milli- 
metre. The stained specimens showed the largest red cells which 
I have ever seen, for the most part perfectly well shaped and natural 
looking, but averaging 12 ji in diameter. This stage is, however, a 
comparatively short one, and the size of the red corpuscles soon be- 
comes normal or subnormal. The abnormal staining reactions and 
the oval forms disappear. As a rule, the count of corpuscles does 
not remain long above 4,000,000, but ranges in the neighborhood of 
3,000,000 during the greater part of the remission. 

3. The Red Cells. Usually the proportion of large forms 
diminishes as in Ehrlich' s case: {a) Active stage; red cells 1,340,- 
000, large forms 66 per cent, (h) Remission; red cells 4,115,000, 
large forms 33 per cent. At the beginning of the remission the 
number of megaloblasts diminishes, while the normoblasts increase. 
Later the latter also disappear. Deformities become less marked 
and the "pessary shaped" cells (pale centres) appear, giving the 
blood the appearance of secondary anaemia. Polychromatophilic 
and sj)otted cells grow less numerous, but Ehrlich maintains that 
the latter may remain even when the blood has otherwise regained 
10 



146 



SPECIAL PATHOLOGY OF THE BLOOD. 



its normal appearance. He therefore considers " spotted red cells " 
of value for diagnosis during remissions. 

The rate of regeneration is often astonishingly rapid. 

In Case YII. of my series the red cells increased from 1,800,000 
to 5,200,000 in fourteen days. In Case XXXIX. the red cells in- 
creased from 2,200,000 to 4,000,000 in thirteen days. In Case 
LVIII. the red cells increased from 1,500,000 to 3,200,000 in 
twelve days. In Case XCI. the red cells increased from 1,700,000 
to 3,000,000 in fourteen days. 

Similar observations have been reported by Ehrlich and other 
observers. 

It is quite possible, although I have no figures to prove it, that 
in the periods of decline the red corpuscles may fall as rapidly as 
they subsequently rise. This possibility is suggested by the fact 
that one rarely sees pernicious anaemia in an early stage — that is, 
until the red corpuscles have fallen below 2,000,000 per cubic milli- 
metre. Only four of my cases showed more than 2,000,000 red cor- 
puscles per cubic millimetre at the time of the first examination of 
the blood. 

Summary. 

The more important characteristics of the blood of pernicious 
anaemia are as follows : 

1. Red cells about 1,200,000 per cubic millimetre. 

2. White cells much diminished. 

3. Haemoglobin variable, 5ome^^me« increased relatively (= high 
color index). 

4. Deformities in size and shape of red cells in many cases. 

5. Increase in average diameter of red cells. 

6. Polychromatophilic red cells. 

7. Megaloblasts more numerous than normoblasts. 

8. Lymphocytosis. 

9. Small percentage of myelocytes. 

The items italicized are the most important and chaTacteristic. 

Diag7iostic Value. 

1. Pernicious anaemia and chlorosis may be indistinguishable 
without the examination of the blood. The pallor of the two dis- 
eases is not always different either in degree or in kind, and the 
symptoms and physical signs may be identical. 



THE PRIMARY ANEMIAS. 



147 



The differential diagnosis is easily made by the blood. The red 
cells rarely reach as low as 2,000,000 in chlorosis and the number 
and degree of degenerative changes are less than in pernicious anae- 
mia. Megaloblasts have been seen in chlorosis (Hammerschlag) 
but have never constituted a majority of the nucleated red cells 
present. In the great majority of cases the pallor and other signs 
and symptoms of chlorosis are due to lack of haemoglobin per cor- 
puscle (for the corpuscles are not only pale but very small-sized), 
and not to a lack of corpuscles. The high color index and large 
size of the scanty cells in pernicious anaemia contrast strongly with 
this. 

The white cells are about the same in both diseases, though 
usually fewer in pernicious anaemia. Lymphocytosis is common to 
both diseases. Myelocytes are occasionally found m chlorosis, but 
much less commonly than in pernicious anaemia. 

2, Fernicious Ancemia and the Ancemia of Malignant Disease. — 
Not long ago I examined the blood of a gentleman who had grad- 
ually and without assignable cause acquired a lemon -yellow " pal- 
lor, without loss of flesh, vomiting, pain, or any localizing sign or 
symptom. The diagnosis of pernicious anaemia had been made. 
To my great surprise I found over 4,000,000 red cells, with only 38 
per cent of haemoglobin, and 18,780 white cells, 86 per cent of 
which were polymorphonuclear neutrophiles. One normoblast was 
seen. Fibrin was not increased. The anaemia was evidently sec- 
ondary, and the autopsy ten months later showed cancer of the 
stomach. 

Osier and McCrae record a case in which the symptoms and signs 
(except the blood) were so suggestive of pernicious anaemia that Osier 
made that diagnosis. Six months later a nodular mass was felt in 
the region of the stomach and the patient soon after died. In this 
case the red cells varied between 2,840,000 and 3,048,000. The 
leucocytes numbered 11, 500 ; there were no nucleated red cells and 
but slight poikilocytosis. Haemoglobin was 25 per cent, i.e., the 
blood of secondary anaemia. I have since had four similar cases. 

Malignant disease may bring down the count of red cells to 
1,000,000 or lower, but in such cases leucocytosis is often present. 
As will be seen in the chapter on malignant disease, leucocytosis is 
by no means invariable in the anaemia of cancerous growth, but in 
those cases which cause such an anaemia as to resemble the counts 
of pernicious anaemia, leucocytosis is the rule. This in itself is 



148 



SPECIAL PATHOLOGY OF THE BLOOD. 



usually sufficient to exclude uncomplicated pernicious anaemia. 
When an increase in the whole number of leucocytes is not present 
in malignant disease, there is often an increased percentage of poly- 
morphonuclear cells, contrasting strongly with the increased per- 
centage of lymphocytes in pernicious anaemia. 

Normoblasts and not megaloblasts are the rule in malignant dis- 
ease. If megaloblasts are present they are in the minority, while 
in pernicious anaemia they are in the majority. The average size 
and staining-power of the red cells is increased in most cases of 
pernicious anaemia and decreased in most cases of malignant dis- 
ease. 

Ehrlich has twice diagnosed pernicious anaemia from the blood 
examination and been confronted at the auto^jsy with small can- 
cerous growths in the stomach. In one case the cancer w^as "the 
size of a hazelnut " ; in the other, an annular fibrous cancer of the 
pylorus without any ulceration." In these cases I believe the can- 
cer to have been a complication and not the cause of the anaemia. 
Such small growths are very rarely associated with any anaemia at 
all. 

Hayem insists that pernicious anaemia may be distinguished from 
aucemia secondary to cancer, because in cancer the .clot contracts 
firmly and squeezes out the serum, and the blood plates are but 
slightly diminished, while in pernicious anaemia the clot does not 
retract and blood plates are greatly decreased. 

3. Pernicious Ancemia and other Secondare/ Amemias. — Most 
secondary anaemias which are severe enough to reduce the count of 
red cells below 2,000,000 follow the type of malignant disease and 
show leucocytosis. The great pallor and dyspnoea seen in connec- 
tion with some cases of tnhei-culosis and ne2)hritis rarely mean a low 
count of red cells, but simply a loss of haemoglobin. I remember 
two cases in adjacent beds at the Massachusetts General Hospital, 
both with extreme yellow pallor without emaciation; one had 
1,020,000 and the other 4,100,000 red cells, the haemoglobin in 
each being about thirty per cent. The first was pernicious anaemia, 
the second nephritis. 

Purpura, typhoid, lead poisoning, chronic malaria, and other 
diseases may reduce the red cells to a point as low as that seen 
in early stages of pernicious anaemia and may not he accompanied 
by leucocytosis; but the absence of changes most characteristic 
of the latter disease (a majority of megaloblasts, increased diam- 



THE PRIMARY ANEMIAS. 



149 



eter and color index in the red cells) serves to make the diag- 
nosis clear.' 

4. Fernicioiis Ancemia and Xe^rA^ffy/w^. — Occasionally in infants 
these two diseases seem to approach very near each other and are 
difficult to distinguish. In infancy, as is well known, any anaemia 
(primary or secondary) is apt to be accompanied by leucocytosis 
and an enlarged spleen. Further leukaemia, which in adults usu- 
ally causes a relatively slight anaemia, affects the red cells much 
more strongly in infancy, and may reduce them to a number de- 
cidedly suggestive of pernicious anaemia. Therefore in both dis- 
eases we may have enlarged spleen, great anaemia, and leucocytosis. 

The one characteristic point of leukaemic blood — the abundance 
of myelocytes — usually enables us to distinguish the two diseases, 
for although present in both diseases the myelocyte is much more 
plentiful in leukaemia. Unfortunately we have no way of fixing 
just how numerous myelocytes must be in order to constitute leukae- 
mia. It is only in infancy and very rarely then that this difficulty 
arises, but at that period I am inclined to believe that we sometimes 
see conditions intermediate between the two diseases, indicating the 
ultimate identity of the two. Their numerous clinical resemblances 
cannot here be discussed. (For further comment on this point see 
page 454). 

Prognostic Value of the Blood in Pernicious Anemia. 

The prognosis is always very bad, but the following scheme in- 
dicates the presence of a severe or of a mild type : 

1. Severe (rapidly fatal). 2. Less Severe {slower course). 

(a) Extreme progressive an- (a) Remissions. 

aemia. (b) Normal or low color index. 

(b) High color index. (c) Normal-sized or small cells. 

(c) Increase in size of red cells, (d) No degenerative change. 

(d) Degenerative changes. (e) Numerous normoblasts. 

(e) Numerous megaloblasts. (/) Few megaloblasts. 

(/) Few or no normoblasts. ( g) Normal percentage of poly- 
((/) Lymphocytosis. morphonuclear cells. 

It has been thought by some observers that the absence or great 

' Another point of difference emphasized by Grawitz is that the plasma of 
pernicious anaemia has a relatively larger amount of solids than that of anae- 
mia secondary to the above diseases. This is hardly a clinically applicable 
test, but is said to be a valuable one. 



150 



SPECIAL PATHOLOGY OF THE BLOOD. 



scantiness of nucleated corpuscles indicated lack of any effort at 
regeneration on tlie part of the blood-making functions and hence a 
peculiarly malignant type of the disease. I have never seen cases 




Fig. 30.— Normal Blood. Masmlfled 350 diameters. 

in which nucleated corpuscles were steadily absent, but their scanti- 
ness has seemed to me as a rule to be associated with a more sloivly 
fatal type of the disease. 

Ko significance has seemed to me to attach to the presence of 
larger or smaller percentages of eosinophiles. 



Red cells 

White cells. . . . 
Haemoglobin . 
Megaloblasts . , 

Normoblasts. . , 



Size of red cells 
Lympliocytes . . . 
Polymorphonu - 

clear cells. 
JVIyelocytes 



Pernicious aneemia. 

About 1,000.000 

Usually decreased 

Often relatively high. . . 
Constitute the majority 

of the nucleated red 

cells. 

Less numerous than the 
megaloblasts. 

Increased 

Increased 

Decreased 

Common 



Chlorosis. 

Rarely under 2,000,000 

Usually normal 

Always relatively low 

Rare 

Occasional ; always more 
numerous than megalo- 
blasts. 

Diminished 

Increased 

Decreased 

Rare 



Secondary anaemia. 



May be 1.000,000 or less. 
Usually increased. 
Relatively low. 
Rare ; never more numer- 
ous than normoblasts. 

Common. 



Various ; not increased. 
Usually diminished. 
Usually increased. 



Rare. 



To illustrate the different size of the cells in chlorosis and per- 
nicious anaemia I have had photographs taken of the blood of a case 



THE PRIMARY ANEMIAS. 



151 




Fig. 31.— Pernicious Anaemia. Magnified 350 diameters. Note the relatively large size and 
well-stained centres of the cells. 

of two of these diseases and of normal blood, all on precisely the 
same scale (see Figs. 30, 31, 32). 




Fig. Chlorosis. Magnilled 350 oiameLciii. iXote small size and pale centres. 



152 



SPECIAL PATHOLOGY OF THE BLOOD. 



2. FATAL ANEMIA WITH HYPOPLASTIC MARROW. 

(^^ AplastiG AncemiaJ^) 

Ehrlich reported in 1888 ' the case of a girl of twenty-one, with 
cutaneous, uterine, buccal, and retinal hemorrhages, which caused 
death within thirty days from the first symptom. Blood examina- 
tion showed 213,360 red cells —small, fairly stained forms predomi- 
nating. Deformities were slight. No nucleated red cells could be 
found despite many hours' search before and after death. Leuco- 
cytes numbered 200 per cubic millimetre — an astonishing leuco- 
penia. Eighty per cent of these white cells were lymphocytes 
and 6 per cent large mononuclears, leaving but 14 per cent (or 28 
per cubic millimetre) of polynuclear neutrophilic cells. In other 
words, the neutrophiles were reduced to about yi^- of their normal 
number, while the lymphocytes were distinctly though less mark- 
edly diminished. Eosinophiles were wanting altogether. 

The great diminution in red cells and granular leucocytes in this . 
case suggested to Ehrlich a lack of compensatory reaction on the 
part of the marrow. Autopsy confirmed this. The marrow of the 
femur was yellow throughout except for a tinge of red near the 
lower end. 

Similar cases have lately been reported by Lipowski and by 
Muir.^ In these as in Ehrlich' s case hemorrhages were prominent. 

The red cells in Muir's case were not increased in size and their 
number was reduced to 800,000 and the haemoglobin to 11 per cent. 
The leucocytes numbered 7,000 per cubic millimetre, but only 25 
per cent of them were polynuclear neutrophiles. Eosinophiles and 
blood plates were entirely absent. No nucleated red cells could be 
found in the blood, and only one or two in the marrow, post mortem, 
despite long and careful search. The marrow was of the fatty tjrpe, 
almost white, and contained few neutrophiles and 7io eosinoj^hiles. 

In Lipowski' s case as in Ehrlich' s and in Muir's the disease was 
dubbed " purpura hsemorrhagica " owing to the profuse hemorrhages 
from mucous, serous, and cutaneous surfaces. The red cells were 
2,112,000, hsemoglobin was 18 per cent. Only 7 per cent of the 
leucocytes were neutrophiles, the rest lymphocytes. Nucleated red 
cells were absent. 

^ Charite-Annalen, xiii. 

2 Lipowski: Deut. med. W^och., 1900, p. 340. 
sMuir: Brit. Med. .lour., 1900, p. 910. 



THE PRIMARY ANEMIAS. 



153 



3. THE BLOOD IN CHLOROSIS. 

This has been already described for the most part under the 
heading of Secondary Anaemia. In many cases the two are indis- 
tinguishable by the blood examination alone, the changes consisting 
simply in the presence of light, small-sized, pale, more or less de- 
formed red cells whose number may or may not be decreased, ac- 
cording to the severity of the case. Leucocytosis is rarely if ever 
present in uncomplicated chlorosis, but is often absent in secondary 
anaemia. Normoblasts may be present in both. The chief points 
of distinction are : 

(«) The red cells are more apt to be uniformly under-sized and 
under-colored in chlorosis, while in secondary anaemia we more often 
find normal cells among the diseased ones. 

(b) The color index may be lower in chlorosis than is common 
in secondary anaemia, and this lowering is more constant in chlorosis. 

(c) Absolute diminution in the number of polynuclear leucocytes 
which is very common in chlorosis, is not so common in secondary 
anaemia. 

(d) Nucleated corpuscles are less common in chlorosis than in 
anaemia secondary to malignant disease. 

(e) Coagulation is rapid, in contrast with the very slow clotting 
of pernicious anaemia and of many secondary anaemias. Yet fibrin 
is not increased. The increased rate of coagulation seems to be 
connected with the marked increase in blood plates, which is almost 
always present. 

Volume and Oxygen CajKicity of the Blood. 

The blood volume is greatly increased. In 21 cases with haemo- 
globin below 50 per cent Smith found the average volume 4,883 c.c, 
or over one-half greater than the normal average (3,240). The vol- 
ume is increased in proportion to the severity of the disease. Some 
cases showed 6,400 c.c. of blood, or nearly double the average. At 
the same time the total oxygen capacity (or total haemoglobin) is 
approximately normal, averaging over 95 per cent in 21 cases. As 
the specific gravity of the plasma is normal, there appears to be a 
great increase in the amount of normal plasma. If we were to 
imagine this excess of plasma filtered off, there would remain {e.g., 
in Case X. of Smith's series with 6,266 c.c. and 2,600,000 red cells) 
about 8,000,000 red cells per cubic millimetre. Hence Smith con- 



154 SPECIAL PATHOLOGY OF THE BLOOD. 

eludes that there is really a large absolute increase in the number 
of red and white cells disguised by an excess of plasma. Under 
treatment the oxygen capacity or haemoglobin is not increased, 
but the amount of plasma diminishes — in one case from 4,574 c.c. 
to 2,800 c.c. If confirmed Smith's results will revolutionize our 
ideas of chlorosis. 

The Blood in Gross. 
The pallor of the drop is sometimes excessive, fully as great as 
in pernicious ansemia, and the liquid is very fluid and thin. Yet 
it coagulates very rapidly and our technique must be prompt. 

Red Cells and Haemoglobin. 

Quantitative Changes. 

Hayem has recorded cases whose count was as low as 1,662,000 
and even 937,360 per cubic millimetre. Such figures are certainly 
rare in this country, and the striking fact is usually the slight nu- 
merical loss of red cells, considering the extreme pallor of the pa- 
tients. 

The lowest count in the Massachusetts General Hospital series 
was 1,932,000, and in W. S. Thayer's 63 cases 1,953,000. The 
accompanying tables, from the Massachusetts General Hospital 
records, show the range of red cells and haemoglobin in 179 cases 
as counted when the patients first came under observation. The 
highest counts (7,100,000 and 5,884,000) are undoubtedly due to 
some temporary stasis or concentration of the blood. 

The average of the 179 cases, 4,700,000 red cells per cubic milli- 
metre, is somewhat higher than in Thayer's' series above referred 
to, the average of which is 4,096,544. 

The average haemoglobin percentage of this series, 41.2 percent, 
is also very close to Thayer's (42.3 per cent). This gives us on the 
average a reduction of the corpuscle substance to one-half the nor- 
mal, or to the equivalent of 2,250,000 healthy red cells; 95 of the 
179 cases have 4,000,000 or more red cells. These figures do not 
agree with those collected by v. Limbeck, in which only 99 out of 
247 are over 4,000,000. But this probably means simply that in 
this country the patients seek medical advice before their disease 
has advanced very far, while in Germany they wait longer before 

' See Osier's article on Chlorosis in the " American Text-Book of Medicine," 
vol. ii., 1894. 



THE PRIMARY ANEMIAS. 



155 



resorting to a hospital. For, as above explained, in all anaemias 
the individual corpuscles suffer in quality first and only after some 
time begin to decline in number. This is especially the case in 
chlorosis, although by no means peculiar to that disease. 

The color index is invariably low, as seen in the table, although 
it is rare to see it fall below .30. In only four cases of the present 
series did it go below that figure, the average being about .50. 

V. Noorden' found that the color index was especially apt to be 
low in first attacks and less often in the recurrent or habitual cases, 
but Romberg,^ in a study of one hundred and seventeen cases, has 
not found this true, and I agree with Eomberg. One of the lowest 
color indexes in my series was in a woman over fifty who had a 
truly habitual chlorosis. 



Table VI. — Chlorosis. 



Red Cells. 
Between 7,000,000 and 8,000,000 



Cases. 
1 



6,000,000 
5,000,000 
4,000,000 
3,000,000 
2,000,000 
1,000,000 



7,000,000 2 

6,000,000 24 

5,000,000 68 

4,000,000 58 

3,000,000 25 

2,000,000 1 

Average of these 179 cases = 4,700,000 



White cells. Cases. 

^6,000 1 

Between 15,000 and 14,000 4 



14,000 
13,000 
12,000 
11,000 
10,000 
9,000 
8,000 



13,000 2 

12,000 8 

11,000 11 

10,000 14 

9,000 12 

8,000 9 

7,000 31 



White cells. 



Cases. 



Between 7,000 and 6,000 29 



6,000 
5,000 
4,000 
3,000 
2,000 



5,000 18 

4,000 15 

3,000 10 

2,000 2 

1,000 2 



Average, 8,000 



168 



Per Cent of Hemoglobin in Chlorosis. 
Between 10 and 19 — 



cases. 





20 ' 


' 29 = 


32 




30 ' 


' 39 = 


48 




40 * 


' 49 = 


38 




50 ' 


' 59 = 


41 




60 


' 69 = 


14 




70 


' 1 = 


1 



183 

Average, 41 per cent, 

»" Chlorosis," Wieu, 1897 (Holder). 
sBerl. klin. Woch., June 28th, 1897. 



156 



SPECIAL PATHOLOGY OF THE BLOOD. 



The striking contrast is with pernicious anaemia, rather than with 
secondary anaemia. In the former the color index, as above men- 
tioned, averaged 1.04 in 68 cases. In secondary anaemia it is al- 
most always below 1, but does not average so low as in chlorosis, 
although in individual cases it may be very low. 

For example, Osterspey quotes a case of gastric cancer with a 
blood count of 4,230,000 red cells, and only 22 per cent of ha?mo- 
gobin, a color index of .26. 

Qua/ if at t re Changes. 

{a) The stained specimen shows a greater or less degree of 
jKilIor of the corpuscle centres corresponding so accurately to the 
diminution in hsemoglobin that a practised observer can tell approx- 
imately how low it is simply from the stained specimen. The 
pallor, however, is to be taken in connection with the size of the 
cells, for the diminution in haemoglobin is not due simply to a 
bleaching out of the cells, but to their loss of size. Hence, 

(h) The dimhvidion in the average diameter of the cells is a very 
important feature. In the convalescent we may watch the gradual 
increase in the average diameter of the cells from 5.5 !>. or lower up 
to 7.9// or even 8.2// (see Appendix C). Both in this respect and 
as regards the bleaching of individual cells, many cases contrast 
with most secondary anaemias, in that a large proportion of the 
cells are affected alike, i.e., are small and pale, while in secondary 
anaemia there are apt to be well-stained and good-sized or over-sized 
cells in every field. These last occur also in chlorosis, but less fre- 
quently as a rule. Hence the usually lower color index of chloro- 
sis. In certain cases this distinction does not hold, and the two 
conditions are identical in so far as the size and color of the red 
cells are concerned. 

(c) Deformities in size and shape are very common in all ad- 
vanced cases, but often absent in mild or moderate ones. They 
present no special peculiarities except that macrocytes are relatively 
rare and microcytes relatively common. In the severest cases, how- 
ever, the macrocytes begin to get more numerous and we approach 
the picture of pernicious anaemia. 

. {d) Degenerative changes (Maragliano, see page 86) are not 
common but are occasionally present in severe cases. 

(e) Nucleated red corpuscles are very scanty even in advanced 
cases. Hayem never saw any, but most observers find them in 



THE PRIMARY ANEMIAS. 



157 



small numbers after long search. They are almost always of the 
normoblast type, but megaloblasts have also been found. In four 
cases of my series normoblasts in small numbers have been found — 
never more than one hundred and twelve per cubic millimetre. I 
have never found megaloblasts. 

The scantiness of nucleated red cells is a point of contrast with 
the anaemia secondary to malignant disease, in which even in mildly 
anaemic states we readily find nucleated corpuscles, while in chloro- 
sis, even in severe cases, a long search may show very few or even 
none at all. 

Specific Gravity. 

Chlorosis is usually agreed to be one of the diseases in which 
specific gravity and haemoglobin run parallel, and as the inaccura- 
cies and inconveniences of the v. Fleischl instrument are so great, 
it seems to the writer better to follow the specific gravity rather 
than the haemoglobin. The tables on page 41 (Part I.) show how 
the inference from density to coloring matter can be made. A 
specific gravity of 1030 is not very rare. 

White Cells. 
A. Qiiantitatice Changes. 

Leucocytosis is absent in uncomplicated cases. In the series in 
Table VI. the occasional leucocytosis may be due to digestive or to 
a variety of other influences (uterine troubles, etc.), which could 
not be excluded. 

The average in Thayer's 63 cases was 8,467 ; in the present series 
(see Table VI.) it is just under 8,000. 

As in pernicious anaemia, the worst cases are apt to have leuco- 
j)enia, and as improvement progresses the white rise even faster 
than the red corpuscles. 

Thus in Romberg's careful study of 117 cases, 24 cases whose 
haemoglobin was under 40 per cent had an average of 6,350 leuco- 
cytes per cubic millimetre, while 52 cases whose haemoglobin aver- 
aged 60 per cent had an average of 9,250 leucocytes. He found 
the average in healthy girls of the same age to be 9,068 white cells 
per cubic millimetre. 

The absence of leucocytosis is the most important point in dis- 



158 



SPECIAL PATHOLOGY OF THE BLOOD. 



tinguishing chlorosis from secondary anaemia due to cancer, suppu- 
ration, etc. 

B. Qualitative Changes. 

Lymphocytosis is usually present, as in pernicious anaemia, when- 
ever the disease is well marked, and sometimes even in mild cases. 
Thus Rieder found in 12 cases an average of 33 per cent of lympho- 
cytes, the highest percentages being 53.7, 43.5, and 41.7. Either 
the small or the large lymphocytes may predominate. In my own 
experience it has usually been the small forms. 

The neutrophiles suffer proportionally, their low percentage con- 
trasting often with that of secondary anaemia associated with leu- 
cocytosis. Eosinophiles are occasionally increased. In Eieder's 
12 cases the average percentage was 3.5, the highest percentages 
being 9.6 and 7 per cent. 

Myelocytes are rare but have occasionally been observed in small 
numbers. 

Regeneration of the Blood. 
As the patients begin to mend under the influence of treatment, 
the blood changes are just the reverse of those seen during the de- 
velopment of the disease. First the corpuscles gain in numbers, the 
haemoglobin still remaining low ; later and much more slowly the 
coloring matter, size, and weight of the cells are renewed. It 
seems as if the new-formed cells were of light weight and had to be 
replaced gradually by cells of normal stature. The nucleated cor- 
puscles and deformities disappear and the leucocytes shoot up often 
a little above the normal. 

Blood Plates. 
They are usually considerably increased. 

Chlo7'osis without Known Blood Changes. 
Romberg quotes the following facts: Three girls, nineteen, 
twenty, and twenty -five years of age, came to him with typical 
symptoms of chlorosis. Their blood counts showed: 

I. Eed cells, 5,246,000; Hb., 80 per cent. 

II. " " 5,376,000; 83 

III. " " 4,408,000; 87 

All improved markedly under iron treatment. 
I mention this because I have seen several similar cases and have 
heard of others from colleagues. 



THE PRIMARY ANEMIAS. 



159 



Summary. 

1. Blood as a whole : Very pale in marked cases, very fluid, but 
coagulates rapidly. Fibrin not increased. Specific gravity usually 
low, running parallel with the haemoglobin. 

2. Red cells: Average 4,000,000 the when patient is first seen, 
very rarely go below 1,000,000. The majority of them are small- 
sized, pale, often deformed. Nucleated corpuscles are rare (normo- 
blasts as a rule). 

3. White cells not increased. 
Lymphocytosis, occasionally eosinophilia. 

4. Blood plates increased. 

Diagnostic Value. 

1. The points of difference from pernicious anaemia have been 
discussed. 

2. It is important to distinguish it from simple debility, and 
from cases in which the skin only is anaemic ; in both of these con- 
ditions the blood is normal. 

3. From secondary anaemia it may be indistinguishable in case 
the latter be without leucocytosis. When leucocytosis is constantly 
present and the percentage of polymorphonuclear leucocytes is in- 
creased, chlorosis (uncomplicated) can be excluded. Of course 
many of the complications which may occur in chlorosis are accom- 
panied by leucocytosis. 



CHAPTER 11. 



LEUKEMIA. 

The distinction between leuksemia and leucocytosis has been 
sufficiently dwelt on above. 

The blood of the vast majority of cases of leukaemia falls clearly 
imder one or the other of two distinct types, myeloid on the 
one hand, lymplioid on the other. Myeloid blood is found only 
in cases with great hypertrophy of the spleen, marked marrow 
changes, and little or no enlargement of the other lymphatic tissue. 
Such cases are usually chronic (two to five years). Lymphoid blood, 
on the other hand, may be associated either with acute or chronic 
forms of the disease, and while in all cases we have some set of 
lymphatic glands enlarged there may be no external^ risible glands 
enlarged, and the spleen may be as big as in cases of the myeloid 
type. The diagnosis of leukaemia can easily be made by the blood 
alone, but we cannot say from the blood whether or not the spleen 
or the visible lymph glands are hypertrophied. In acute cases the 
lymph glands of the alimentary tract (cervical, faucial, gastro- 
enteric, mesenteric) may be the only set involved. 

All of the thirty-seven cases associated with myeloid blood which 
have come under my observation have run a chronic course, while of 
the cases showing lymphsemia seven were chronic, five acute, and 
five subacute. All the myeloid cases had very large spleens with- 
out enlargement of visible lymph glands, but three of the lymphatic 
cases had spleens almost filling the abdomen. 

The disease leukaemia, then, is associated with two types of 
blood. 

1. Myeloid blood. 

2. Lymphoid blood. 



LEUKEMIA. 



161 



I. MYELOID LEUKEMIA. 

The drop as it emerges from the puncture looks somewhat 
opaque in color, but is neither whitish nor chocolate colored. It 
flows very sluggishly, however, and is difficult to spread between 
cover-glasses owing to the masses of white cells contained in it. 
Coagulation is normal, three minutes or less with Wright's coagu- 
lometer, and fibrin is not increased. 



Eed Cells. 

In the earlier stages of the disease there is no anaemia. Later 
the diminution in red cells is moderate, averaging about 3,120,000 
in the forty-seven cases of Table VII. Toward the end of life 
the count of red cells often falls below 2,000,000. The patients 
are often not loale and may feel perfectly well. The haemoglobin 
is usually diminished, the color index being about 0.6 in my cases. 
It is difficult to read the v. Fleischl instrument in leukaemia, as the 
presence of so many leucocytes gives a muddy tint to the liquid, 
not easy to compare with the red of the glass. 



Table VII. — Leukemia. 



No. 






Highest. 

























































































Red cells. 



5,000,000 
4,877,000 
4,800,000 
4,592,000 
4,288,000 
4,140,000 
4,016,000 
3,760,000 
3,635,570 
3,605,000 
3,400,000 
3,292,000 
3,200,000 
3,170,000 
3,090,000 
3,080,000 
3,020,000 
3,078,000 
3,010,000 
2,996,000 
2,960,000 
2,952,000 
2,938,000 



11 



No. 






Highest. 























































































White cells. 



1,072,222 
980,000 
820,000 
800,000 
756,000 
748,000 
716,000 
656,000 
626,600 
570,000 
500,000 
492,000 
454,000 
453,000 
448,000 
430,000 
428,000 
405,000 
400,000 
394,000 
386,000 
367,000 
340,000 



162 SPECIAL PATHOLOGY OF THE BLOOD. 



Table VII.— Leukemia {Continued). 



No. 




Red cells. 


No. 




White cells. 


O A 




2,921.600 
2,868,000 
2,792,000 
2,738,000 
2,715,000 
2,706,000 
2,576,000 
2,520,000 
2,500,000 
2,322,222 
2,320,000 
2,256,000 
2,140,000 
2,112,000 
2,060,000 
2,016,000 
2,010,000 
1.866,664 
1,756,000 
1,420,000 
1,386,000 
1,358,000 
1,200,000 
408,000 

3,131,000+ 


O 1 




324,000 
320,000 
290,000 
290,000 
260,000 
260,000 
248,000 
220,500 
213,000 
188,000 
186,000 

-i QO AAA 

183,000 
175,800 
170,000 
141.000 
139,600 
138,000 
134,400 
132,000 
111,000 
98,000 


OK 




ok; 




Of? 




OA 




OT 




0'7 




OQ 




9Q 




oo 




00 




QA 




Qn 




Q1 




Q1 




QO 




QO 




QQ 




QQ 




Q ( 




Q/i 




ox 












36 




Q7 




37 




38 




38 




39 




39 




40 




40 




41 




41 




42 




42 




43 




43 




44 




44 


Lowest. 








46 




Average = 428,000 


47 


Lowest. 
Average = 





Qualitative Changes. 
The striking point is the presence of very numerous nucleated 
red cells, even in the absence of any sign of anaemia. With over 
4,000,000 well-formed and w^ ell-colored red cells, we may have 
hundreds of erjrfchroblasts in every cover-glass. They are as nu- 
merous in this form of leukaemia as in the worst forms of pernicious 
ansemia, even though the patient may be feeling nearly well. In 
Taylor's cases there were ten with 10,000 or less of the nucleated 
red cells per cubic millimetre, three with 10,000 to 20,000, and two 
between 60,000 and 70,000. One showed only 360 per cubic milli- 
metre. 

Both normoblasts and megaloblasts may be seen, but in most 
cases the latter are in the minority. Many of the normoblasts 
show fragmentation in their nuclei, and occasionally true karyoki- 
netic figures are seen. In the ansemic cases we find all the other 
changes in the red cells characteristic of anaemia, but the nucleated 
cells are almost always more prominent than in any other form of 
ansemia of a like severity. This shoAvs that nucleated corpuscles 



PLATE II. 



Fig. 1. — Both this and Fig. 2 are intended to be f ac-similes of actual micro- 
scopic fields. 

(a) Note the cell between those labelled 8 and 9— apparently a "mast cell." 
Such cells are often seen in this form of leukaemia. With Ehrlich's stain they 
present this appearance. Basic stains bring out coarse blue granules in the 
periphery of the protoplasm. 

(b) Note also the cell at the extreme upper right-hand corner of Fig. 1, 
which it is almost impossible to classify either as a myelocyte or as a poly- 
morphonuclear neutrophile, since it aj)pears to be intermediate between the 
two varieties. 

(c) Both the nucleated corpuscles are normoblasts ; 9 has polychromatophilic 
protoplasm. The red cells show scarcely any deformities and very slight de- 
ficiency in coloring matter. 

Fig. 2. — («) Note the deformities in size and shape of red corpuscles, owing 
to the anaemia present. 

{h) No lymphocj^tes are figured, as they made up only two per cent of the 
white cells in this case. Eosinophiles were absent. 

(c) Note that the contrast between this figure (leucoc3^tosis) and the one 
above it (leukaemia) is not in the abundance of white cells but in the kind of 
white cell predominating among those present. 



Examination of the Blood. 



PLATE n. 



Figure I = Splenlc-myelogenous Leucaemia 
Figure II = Leucoeytosis (cancer of kidney) 
Cells stained yellow = Eed corpuscles 

1. 2, 3. 4 a. 5 = Polymorphonuclear neutrophiles 

6 ^ Lymphocyte 

7 a. 8. = Eosinophiles 

9 a. 10 = Nucleated red corpuscles 





R. C. Cabot fee. 



Lith, Anst. t. E. A. Funke, IiOipzig. 



LEUKEMIA. 



163 



are not to be thought of as evidence (like deformities in shape) of 
regenerative or degenerative conditions only. A special connection 
to the wide circulatory channels of leuksemic marrow is very clearly 
indicated, all the more so as in the lymphatic form of the disease 
in which the bone marrow is much less affected, nucleated corpus- 
cles are much less numerous, appearing in relatively small numbers 
in the very acute anaemic cases and not at all in those which are not 
anaemic. The protoplasm of the erythroblasts is usually polychro- 
matophilic, contrasting in this respect with the acidophilic proto- 
plasm of embryonic and infantile erythroblasts. 

The variations in size and shape correspond to the degree of 
anaemia present; occasionally, i.e., in cases seen early in the course 
of the disease, the red cells are quite normal. 

As the count of the white cells rises, that of the red may fall, 
and vice versa ; or the red cells may remain at a comparatively high 
figure despite the progress of the white. 

White Cells. 
Quantitative Changes. 

The average number per cubic millimetre in the forty-four cases 
of Table VII. (the lymphatic cases being excluded) was 438,000 
at the time when the cases first came under observation. The high- 
est count in this series is 1,072,222 and the lowest 98,000. 

Among the older recorded cases are some in which the white 
cells were said to be more numerous than the red. The average 
ratio in my series is about one white to seven red. The highest 
ratio is 1:2, and the lowest 1 : 37. It is best to use the " red 
counter " with a dilution of 1 : 200 in counting the white cells, other- 
wise they are often too crowded for convenience. Hayek ' has shown 
that the count of leucocytes may vary enormously in a very few 
hours; e.g, 10 a.m., 122,500; 4 p.m., 235,000; or again, 10 a.m., 
730,000; 4 p.m., 547,500. 

In the fresh specimen we notice that a large proportion of the 
white cells are but slightly amoeboid, a point of marked contrast 
with leucocytosis, in which the leucocytes are actively amoeboid. 
This is due to the fact that the myelocytes which form so large a 
portion of the leucocytes in this disease possess little power of 
amoeboid motion. 

' Hayek: Wien. klin. Woch., 1897, Ko. 20. 



164 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table YIII. — Myeloid Leukemia. 



2,010,000 
1,720,000 

4,125,000 

4,016,000 
4,592,000 

2,960,000 
8,184,000 
3,156,000 
3,400,000 
3,670,000 
3,100,000 
3,080,000 
2,520,000 



4,016,000 

2,792,000 
2,715,000 
2,256,000 
4,288,000 
2,921,600 
3,010,000 
2,996,000 
4,800,000 
3,060,000 
2,016,000 
2,576,000 
2,448,000 
2,120,000 

2,528,000 
5,120,000 
5,000,000 
4,800,000 
4,140,000 
2,825,000 
2,175,000 
2,952,000 
3,090,000 
3,020,000 



3,170,000 

2,708,000 

2,002,000 
2,631,000 



716,000 
732,000 
708,000 
253,900 
200,000 
646,000 
448,000 

175,800 
264,000 
276,000 
111,000 
183,090 
430,000 
405,000 
510,000 
528,000 
570,000 
560,000 
800,000 
26,000 
139,600 
394,000 
340,0<)0 
213,000 
492,800 
188,000 
134,400 
220,500 
274,000 
260,000 
748,000 
168,800 
190,000 
188,600 
159,000 
134,000 
137,800 
138,000 
141,000 
410,000 
441,000 
324,000 
186,000 
454,000 



260,000 
317,000 
290,000 
260,000 
278,000 
289,000 



Percentage, 



58 



II 
Is 



40.0 



;)6 .-0 
46 
46 
17 



27.2 
31 



55 



'4.2 



35 
40 
31 
31 

35133 
31' 



1.0 



10.5 
15 



18.9 
1.5 
3.8 
2.2 
3 

23 
1.5 
1.5 

10 



3 
17 
2 
5 

1.2 

2 



10.0 



4.5 
14.5 
10.4 
11 



3.8 

0 

6 

0.5 
1 

11.5 
1 

0.5 

3 



2.2 

'2 

18 
5 

3.2 

2.6 



1.2 
1.4 

13 
12 
12 



4.0 



4 

1.5 
2.2 
19 



6.1 
2.5 
1. 
14. 

3 
8 
4 

3' 
5 
1. 

3 



2.8 



2.5 
31 



4.2 



42.0 



28 

33.5 

36.7 



25 



17.4 
42.4 



34 



24.4 
51 

30.3 

18 

33 

26 

48 

33 

42.5 
60 
50 
46 



15 



3.8 



Many 



Many 
Many 



Many 



Many 



Many 



Many 



Many 



Many 



15 



a S 
M be 



Many 



^ S 
be 



Many 



Date. 



Nov. 1st, 1897.1 
Nov. 3d, 1897. 
Nov. 12th, 1897, 
July 16th, 1895. 
July 25th. 1895. 
Jan. 21st, 1897. 
Feb. 8th, 1897. 
Feb. 17th, 1897. 
July 15th, 1897. 
July 29th, 1897. 
Aug. 5th, 1897. 



Aug. 10th, 1896. 

Aug. 31st, 1896. 

Jan. 22cl, 1896. 

Jan. 22(1, 1896.2 

Jan. 23(i, 1896. 

Jan. 24th, 1896. 

June 4th, 1894. 

Aug. 10th, 1894. 

April, 1893. Later 
the count of 
leucocytes was 
normal for sev- 
eral months. 



Jan. 22(1, 1896. 
June, 1897. 



Feb. 22cl, 1896. 
Feb. 25th, 1896. 
Feb. 28th, 1896. 



5.4 per cent, of the 
lym phocytes 
have the char- 
acteristics of 
Tiirck's Rei- 
zungsformen." 

Oct. 4th, 1899. 

Oct. 21st. 
Nov. 3d. 
Nov. 19th. 



' Many cells on border-line between large lymphocytes and myelocytes 
and between these and polymorphonuclear neutrophiles. 
2 Cerebral hemorrhage. Death January 25th, 1896. 



LEUKEMIA. 



165 



Table VIII. — Myeloid Leukemia {Continued). 















Percentage. 






02 








































a> 


m 

-2 


>i 








m 
OJ 


Normoblasts seen wl 
counting them. 


Megablasts seen wt 
counting them. 




i 


Red cells. 


White cells. 


c 
S 
o 
bt 
o 

s 


Polymorphonu( 
neutrophile! 


Small lymphoc: 


Large lymphoc 


Eosinophiles. 


Myelocytes 


Basophiles. 


Transitional 

neutropl 


Date. 


27 


1,756,000 


347,900 


23 


35 


3 


5 


2 


54 


0 




2 


3 


First day. 
Phthisis also 


418,000 
248,000 


41 


2 


6 


2 


48 


0 




11 


4 


38 
29 


2,500,000 




27 
32 


2 
4 


0 

4 


9 
5 


23 
55 


45 




4 


2 


fourth day. 
Tiirck's "Rei- 
zungsfor men" 
9.5 per cent. 


30 
31 








49.6 
30 


3.6 
10 

8 


2.2 

5 


6 
5 


38.6 
45 


10 








32 








54 


0 


5 


34 










33 
34 
35 
36 








47.5 

36 


24.5 
4 


5 
4 


1.5 

28 


27.5 

28 


















57.5 
42 


0 

5 


1.5 

3 


3.7 
1 


36 
47 


1.5 
































Av. 


3,120,000 


348,000 


52 


46 


6 


4.6 


5.1 


35 


5 











With or without the influence of therapeutic agencies or after 
splenectomy the white cells may fall gradually to normal and re- 
main there for some time. The patient's symptoms may simulta- 
neously ameliorate, or there may be no improvement but rather the 
reverse. Such a case occurred under my observation, and the pa- 
tient, a washerwoman, went back to work and afterward passed 
through an attack of lobar pneumonia in safety. 

. At such a time, when no increase in the white cells is present, 
we should never suspect leukaemia, seeing the case for the first time, 
unless we chance to make a differential count ; then the character- 
istic qualitative changes (see below) may be found, or the blood 
may be wholly non-leuksemic, as in a case recently reported by Mc- 
Crae, and in a similar case slides from which were recently shown 
me by Martin. 

Qualitative Changes. 
1. Myelocytes. 

The enormous number of myelocytes is the chief point of inter- 
est. The average in my 36 cases was 35 per cent (see Table VIII.), 
rising in one case as high as 55 per cent and only thrice falling lower 
than 20 per cent. 



166 



SPECIAL PATHOLOGY OF THE BLOOD. 



Taking the average total number of leucocytes as 348,000 per 
cubic millimetre, the absolute number of myelocytes averages over 
120,000 per cubic millimetre. So far as I am aware the highest 
count of myelocytes in any other disease is that mentioned on page 
393 in a case of malignant disease, namely, 4,514 per cubic milli- 
metre.^ The contrast is sufficiently striking. I wish to insist upon 
this point, namely, that the blood of myeloid leukaemia is absolutely 
peculiar and characteristic, and could not possibly be confused 
with that of any other disease. Certain writers of late years have 
concluded that because myelocytes do occur in a great variety of 
diseases other than leukaemia, therefore there is nothing peculiar 
about the blood of the latter affection. It would be as logical to 
say that because albumin and casts occur occasionally in the urine 
of persons practically well, therefore there is nothing characteristic 
about the urine of acute nephritis. 

At the first glance the stained specimen of leukaemic blood seems 
to be composed mostly of myelocytes, but this is because they are on 
the average so much larger than the other forms of white cells, which, 
being packed away in the interstices between the large myelocytes, 
do not appear prominently at first sight. 

Although (as just mentioned) the average size of the myelocytes 
is greater than that of any other kind of leucocyte, there is a great 
range of variation in their size, and some are hardly, if at all, larger 
than a red cell. (This is equally true of the myelocytes as seen in 
the bone marrow. See above, page 71.) 

The individual characteristics and variations in the myelocytes 
have been already sufficiently described on page 69. 

2. Polymorj)]i07iuGlear Cells. 

Absolutely the number of these cells is greatly increased, al- 
though the number in each 1,000 leucocytes is considerably dimin- 
ished. The actual number per cubic millimetre averages over 200,- 
000 in my series, and in all but one of Taylor's 17 there were 
65,000 or more. The average percentage in the thirty- six cases of 
Table VIII. is 46, the figures ranging between 17 and 72 per -cent. 

The individual cells show a much greater range of variation in 
size, staining properties, and the size and shape of the nucleus than 
in any other condition. In most forms of leucocytosis, for example, 

^ Taylor reports a gastric cancer with 4,285 per cubic millimetre. 



LEUKEMIA. 



167 



one polynuclear cell looks very miicli like another, but in this form 
of leukaemia we are often struck by — 

(a) Very small cells or very large cells (4// to 20 p. in diameter). 

{h) Darlz stained or yqyj jjale stained cells. 

(c) Unusual shapes in the nuclei. 

(d) Variations in the size and staining of the granules. While 
normal polynuclear cells have granules nearly of one shade, the 
leuksemic polynuclear cells have granules varying from yellow or 
pink to purple or blue. Their size also varies greatly. Taylor 
found some as large as eosinophilic granules. 

Besides these variations we often see cells apparently belonging 
to this type, but whose protoplasm shows no color or granulation 
whatever. Other cells show a few granules scattered about against 
a perfectly white background. Such cells may contain basophile 
granules beside the neutrophile. 

(e) There are always some cells on the border-line between the 
polymorphonuclear and the myelocyte, and in regard to which de- 
cision must be arbitrary. I have lately been in the habit of classi- 
fying such cells as Transitional Neutropliiles. Similar cells are 
found in leucocytotic and anaemic blood (see page 110). 

S. Lymphocytes. 

In percentages the lymphocytes are reduced from their normal, 
20 to 30 per cent, to an average of 10.6 per cent, as in leucocytosis. 
But still if we class together large and small forms, their absolute 
number is always increased. Thus the lowest percentage present 
in Table VIII. (namely, two per cent) would mean 8,760 out of the 
average 438,000, the total leucocyte count per cubic millimetre, and 
8,760 is three or four times as many lymphocytes per cubic milli- 
metre as are present in normal blood. 

The proportion of large and small forms among the lymphocytes 
varies a great deal. Sometimes the small lymphocytes in this form 
of leukaemia do not differ from those of normal blood either in abso- 
lute number or in type, but in most cases we find large numbers of 
the following atypical varieties : 

{a) Large lymphocytes with a protoplasm so darkly stained that 
it is difficult to distinguish them from myelocytes. Indeed in some 
cases when hints of a granular look appear in the violet-stained 
rim we find it impossible to be sure whether we are dealing with a 
large lymphocyte or a myelocyte. The personal equation alone de- 



168 



SPECIAL PATHOLOGY OF THE BLOOD. 



cides. These cells are not peculiar to leuksemia. Tiirck has de- 
scribed them (under the name of Reizungsformen^^) in most infec- 
tious diseases, and I have often seen them in the blood of malignant 
disease and of pernicious ansemia. Taylor and Weil class them 
as myelocytes without granules. 

(b) Cells like lymphocytes except that they contain from three 
to ten widely separated granules of one or more varieties (basophilic, 
acidophilic, or neutrophilic). 

^. Eosinophiles. 

Like all the other varieties these are absolutely much increased. 
Relatively — by percentages — they may or may not be so. In my 
series they ranged from 1 to 19 per cent, averaging 5. 1 per cent, a 
slight increase over the normal. 

Many writers, wrongly interpreting Ehrlich's observations on 
this point, have stated that an increased jjercentcuje of eosinophilic 
cells was the distinguishing mark of leukaemia, and even recent 
writers (e.^., Gilbert, Strtimpell) continue to repeat this false state- 
ment. 

The cell most cliar act eristic of siolenic-myelogenous leukcemia is 
not the eosinophile but the myelocyte. Nevertheless eosinophiles are 
enormously increased absolutely and this fact may be of great diag- 
nostic value. In a case of cancer of the marrow with ansemia and 
leucocytosis Epstein' found large numbers of myelocytes and nu- 
cleated red cells but no eosinophiles. The absence of eosinophiles 
in this case sufficed to exclude leukaemia. 

We distinguish several types of eosinophiles in leukaemic blood. 

i^a) Ordinary (polymorphonuclear) eosinophiles. 

(b) Eosinophilic dwarf cells and giant eosinophiles. In some 
of these the granules are also huge — even 2 in diameter (Taylor). 

(c) Eosinophilic myelocytes. 

{a) Needs no comment; (b) is simply a very small cell with 
eosinophilic granules ; sometimes such cells are not over 5 ij. in di- 
ameter. They are not uncommon in this form of leukaemia and are 
very rare in any other disease. The same is true of (c), the eosino- 
philic myelocytes which are very rare in any other disease, except 
pernicious anaemia, in which they are occasionally seen. 

These cells are like myelocytes except that their granules are 
eosinophilic instead of neutrophilic (see Plates I. and II.). They 
^Epstein: Zeit. f. kliu. Med., 1896, vol. xxx. 



LEUKEMIA. 



169 



are found in the marrow in considerable numbers and may con- 
stitute the majority of the eosinophilic cells in this form of leu- 
ki3emia. Occasionally we see eosinophiles with a few basophilic or 
neutrophilic granules as well. Eosinophilic myelocytes are of con- 
stant occurrence and great diagnostic value in leukaemia. In no 
other disease are they equally numerous. Their size, like that of 
the neutrophilic myelocytes, varies from 8 to 25 ij. diameter. 

6. Basophiles. 

(a) The lymphocytes may contain basophilic granules as in any 
ordinary blood. 

(b) The basophilic or amphoteric tendency of the granules of 
some of the myelocytes has been already described (p. 69). 

(c) " Mastcellen " or coarsely granular basophiles, usually with a 
trilobed nucleus, are almost always to be seen in specimens stained 
with thionin or methylene blue. With the triple stain their proto- 
plasm is nearly unstained, but usually a number of round wh ite spots 
can be made out against a faintly stained background. These are the 
basophilic granulations. Mast cells make up from one to ten per cent 
of the leucocytes in most cases of myelocytsemia. Ehrlicli states 
that they are always present and greatly increased in such cases, 
but my experience and that of Taylor do not confirm this. In 2 
of Taylor's 11 cases mast cells were absent. On the other hand, 
one of his cases showed over 140,000 mast cells per cubic millimetre 
(10 per cent), and it is undoubtedly true that "an excess of mast 
cells is one of the most trustworthy signs of myelogenous leukaemia." 
Their granules are not purely basic but metachromic. 

6. Mitoses. 

Leucocytes showing mitosis are very rarely found in leuksemic _ 
blood and play a negligible part in the increase of the circulating 
leucocytes. They have no value in diagnosis. 

7. Polymorphous Condition of the Blood. 

Weiss has rightly insisted on the fact that in this type of leukae- 
mia the blood preparations show a very polymorphous condition. 
There are no fixed types, but every variety shades through 
intermediate forms into some other variety. No two cells are 



170 



SPECIAL PATHOLOGY OF THE BLOOD. 



alike. Precisely tlie same conditions obtain in the normal marrow, 
and we can scarcely resist the impression that in this form of leu- 
kaemia we see in the blood unfinished cells of various kinds which 
usually do not appear in the circulating blood. 

As Charcot-Leyden crystals have no diagnostic value and are not 
peculiar to any disease, no description of them will be given here. 
They appear to be present wherever eosinophiles are plentiful, e.g., 
in asthma, gonorrhoea, in the bone marrow, etc. 

8. Remissions. 

During remissions, when the leucocyte count may fall to normal, 
the percentage of myelocytes usually remains large and the diagnosis 
could thus be made even if we saw the case then for the first 
time. This I have observed in two cases, and Thayer and Taylor 
have had the same experience. But occasionally myelocytes and 
all other evidence of leukaemia disappear, and diagnosis in such re- 
missions is impossible. McCrae and Martin have studied such 
cases. 

II. LYMPH^MIA. 

(Lymphatic Leukcemia.^ 

Although Fraenkel once maintained that all cases of lymphatic 
leukaemia are acute, and that therefore the difference between the 
various forms of the disease rests simply on the rapidity of the proc- 
ess in the blood and clinically, there is no doubt that chronic 
lymphatic leukaemia exists. 

Fraenkel was enabled to maintain his position only by extending 
the term acute to cover all cases in which sj'mptoms lasted not more 
than four months. Six weeks is the limit agreed upon by most 
other observers. 

The writer has watched seven cases of typical lymphatic leukae- 
mia for periods of from seven months to three years. In one the 
symptoms were very mild, and the patient came over thirty miles 
from time to time to report at the Out-Patient department. His 
blood showed little variation from the following figures : Bed cells, 
2,300,886; white cells, 112,000. 

The differential count always showed the overwhelming majority 
(over ninety per cent) of small l3riiiphocytes characteristic of the 
disease. The lymph glands were all much enlarged, the spleen just 



PI.ATE III. 



(a) Chronic Lymphcemia with Excess of Small Lymphocytes. 

One polymorph Dnuclear cell is present. All the rest are lymphocytes and 
exemplify the variations in the morphology of the cell occurring m this and 
other diseases as well as in health, e.g., variations in the staining of the proto- 
plasm and nucleus, indentation and even division of the nucleus. 

Xote that the scale of the whole of Plate III. is larger than in the other 
plates (see scale of u). 

(b) Acute Lymphcemia with Excess of Large Lymphocytes. 

Note the lack of chromatin in both nuclei and protoplasm of large lym- 
phocytes. The plasma around them or their extreme edge took most of the 
stain. The brown tint of the red cells is due to underheating. Compare the 
colors with those in the figure above {a) in which the preparation was prop- 
erly heated. 




Lymphatic Leucaemia 

a. Small 1 ..\ nipliocytos in excess 



It- ('. Cabot fee. 



Lith. Aust. v. E. A. 



LEUKEMIA. 



171 



palpable. The patient kept about his work as a gardener for over 
two years. Another in an active wine merchant was wholly unat- 
tended with symptoms. The patient first sought advice for the un- 
sightly glands in his neck. He continued to feel absolutely well 
and to work hard until life was suddenly cut short by an attack of 
pneumonia. I watched his blood for three years, and it always 
showed typical lymphsemia without anaemia. Grawitz has watched 
a similar case for over four years. 

The blood of acute lymphsemia differs as a rule in many cases 
from that of the chronic types. These differences will be referred 
to later on. 

Eed Cells. 

The count of red cells is often somewhat lower than in the 
splenic-myelogenous form of the disease, averaging 3,600,000 in my 
cases. In acute cases it is usually very low and the anaemia pro- 
gresses rapidly. In the infantile cases collected by McCrae, the 
highest count was 2,350,000. In chronic cases the red cells behave 
about as in myelocythsemia, except as regards nucleated forms. 

The chief point of interest is the conq^arative rarity of nucleated 
red cells, the abundance of which is so marked a feature of splenic- 
myelogenous leukaemia. They may follow the grade of anaemia 
present. In other cases (as in one reported by McCrae) nucleated 
red cells are entirely absent, despite a reduction of the red cells to 
1,680,000. In the eleven cases in infants collected by McCrae, 
there were no nucleated red cells found in seven. In acute cases the 
number of nucleated forms is often greater and may be as great as 
in myeloid leukaemia. Two cases recently reported by Herrick ' 
exemplify this. 

White Cells. 
Quantitative Changes. 

As a rule the numerical increase is not so marked as in the 
splenic-myelogenous form. The average ratio of white to red cells 
is about 1 : 50 instead of 1:7, and we rarely see counts reach the 
height common in the other form of the disease. The highest 
count of my series was 1,480,000 at the patient's first visit, and the 
lowest 30,000, the average being 350,000 as compared with 438,000 
in the myeloid leukaemia. These figures refer to uncomplicated cases. 
^ Journal of the American Medical Association, July 24th, 1897. 



172 



SPECIAL PATHOLOGY OF THE BLOOD. 



Qualitative Changes. 
1. Lymphocytes (small forms, large forms, or a mixture) make 
up usually over ninety per cent of all the leucocytes present. In 
some cases tliey are all nearly of one size, while in others we find 
every gradation from the smallest to the largest, so that it is abso- 
lutely futile to attempt to separate them into " large " and " small. " 
Four of my cases were made up wholly of the small forms, all under 
10 II in diameter, two were composed largely of forms over 15 jj. in 
diameter, while six showed every intermediate size. 

Table IX. — Lymphatic Leukemia. 



Red cells. 



4,877,000 
912,000 
1,440,000 

1,336,000 
1,100,000 

3,000,000 
3,500,000 
3,(308,000 



4,700,000 
3,100,000 



2,960.000 
4,160,000 
2,768,000 



3,520,000 
2,653,000 



2,477,500 
4,078,000 



4,196,(KX) 
2,612,000 
3,283,000 

5,837,000 
5,630,000 



2,500,000 
5,178,000 



White 
cells. 



132,000 
23,000 
43,61X) 

92,000 
120,003 

31,600 
31,500 
28,.5(X1 
40,000 

31,500 
40,000 
3,400 

800 
l,48O,O0O 
80,000 
77,500 
51,800 

79,500 

64,000 
164,000 



167 500 
90,200 
738,000 
708,000 
722,000 
760,IK)0 
176,000 
393,000 

124,000 
180.000 
500,01)0 
800,000 
800.000 



20,000- 
60,000 



20 



40 



41 



75.8 
15. 



25.4 



... 68.5 
55 78. 
55 95.3 



95 



95.5 
39;"' 



94.7 
87.9 
80.5 
88.7 



90.4 



94. 



98.6 



99.2 
98.1 
61.4 
50. 

94. 
98. 
97. 
99. 
99.99 



80-90 



c 
£ 



'3.2 



28 

15.6 



12. 
2.1 
1.6 



1.4 



92.3 



1.2 

34 



CP 



2.4 



5.3 
.1 
17.2 
9.4 



8. 



3.2 



.o 
4.6 
2.8 

6 

1.9 

3 

8 

0001 



5-8 ,10-15 



1.6 



Remarks. 



Subacute ; ten weeks. 

Jan. 24th, 1896. 

Jan. 26th, 1896. Acute 

two weeks. 
Jan. 27th. 

Jan. 28th. Death ; au- 
topsy. 
April 3(1, 1896. 
April oth, 1896. 
April 6th, 1896. 
ipril 7th, 1896. Acute: 

live weeks. 
April 8th, 1896. 
April 12th, 1896. 
April 22d (sepsis — semi- 
comatose) . 
April 2i;th. Death. 
March 21st, 1897. Chronic. 
Oct. 26th, 1896. Chronic. 
Nov. 5th, 1896. 
Nov. 7th, 1896. 
Nov. 15th, 1896. 
Nov. 17th. Died Decem- 
ber, 1897. 
Chronic. 

Positive Widal reaction, 
typhoid ? — 1,000 leuco- 
I cytes counted. 
. . Second day. 
.. Third day. Death. 
0 Julv21st; 500 cells counted. 
.. July 23d. 

0 Auff. 5th; 500 cells counted. 

0 Oct.; l,( 00cells counted. 

0 ;0ct. 23d; 500 cells counted. 

0 Nov. 16th; 500 cells 
I counted. 

0 'Nov. 24th, 1898. 

0 'Mav 26th, 1900. 

0 Sept. 2Sth, 1900. 

0 I Nov. 23d, Vm. 

0 One polynuclear In 8,000! 
All the I'est — lympho- 
cytes. 

Examined once a month 
for three years ; excellent 
health throughout ; died 
of pneumonia, Feb., 1901. 



LEUKEMIA. 



173 



Table IX. — Lymphatic Leukemia. — Continued. 



No. 


Red cells. 


White 
cells. 


G 

11 

« tL 
!- C 


Small 
lymphocytes. 


Large 
lymphocytes. 


^-r SO 

|£ 

Si 


CO 

a; 

S 
& 

fl 
""8 


: : M Myelocytes. 


1 

Norrnoblasts. 


: : : 1 Megaloblasts. | 


Remarks. 


14 .... 






'io' 

40 


94. 

97.9 

86.2 

72 

99^6 

92.2 

99.8 

80.2 


7. 

■ V ' 
15. 


5.7 
1.4 
9.8 
28. 

.4 
7.8 

.2 

4.2 




Chronic. 
Acute. 

History unknown. 
History unknown. 
History unknown. 
History unknown. 
2,500 cells counted. 


15 




16 




Ti ... 














18 








Few. 














20 , , 


700,000 
3,600,000+ 


600,fX)0 
350,000+ 






3 




Av'age 


.2 


.4 



* Large and small forms counted together on account of the impossibility of differentiating 
them In these cases. 



In acute cases, in which the large cells usually predominate, the 
staining is often very faint throughout the nucleus and protoplasm 
(see Plate III., h), so that at first sight we should think something 
was wrong with our technique. Other forms of leucocytes in the 
same preparation, however, will stain normally, showing that the 
trouble is in the lymphocytes and not in the technique. These 
large lymphocytes are identical in their appearance with those found 
at the " germ centres " of all adenoid tissue, and probably are the 
mother cells of the small lymphocytes. Benda has termed them 
" lymphogonien." They have often been mistaken for myelocytes, 
from which they are to be distinguished by the absence of any neu- 
trophile granulation. They often show evidences of degeneration 
(see above, p. 70). The protoplasm maybe entirely unstained as 
in most of the cells in Plate III., or it may stain pale gray or 
pink. In other specimens, especially those of the small-cell type 
(Plate III., a), the lymphocytes stain well. Their nuclei are fre- 
quently indented or even divided in two (this occurs also in normal 
blood, but less often). 

Fraenkel believes still that lymphsemia, though not always acute, 
is usually so, and that if a chronic case takes on acute symptoms the 
blood becomes more lymphsemic, while if a case starts acute and be- 
comes chronic the lymphocytes decrease. Thus a case reported by 
V. der Wey' of chronic myeloid leukaemia six weeks before death 
began to have fever, hemorrhages, great increase in the total leuco- 
cyte count and in the anaemia. No complication was present. The 

■Deut. Arch. f. kiln. Med., vol. Ivii. 



174 



SPECIAL PATHOLOGY OP THE BLOOD. 



lymphocytes increased 30 per cent, and the polymorphonuclear 
neutrophiles dropped from 30 co 3 per cent. 

Gerhardt ' watched a case which began acutely with a large 
percentage of large lymphocytes and then became chronic with a pre- 
dominance of small lymphocytes. 

In acute cases Litten^ has noticed fatty degeneration in the 
leucocytes. 

The following figures illustrate the influence of a septicaemia 
(from suppurating cervical glands) which ended the life of No. 3 in 
the above Table IX. 



Date. 



Number 
of leucocytes. 



Percentag'e of 
lymphocytes. 



April 3d.. 
" 4th. 



6th 

8th 

10th 

12th 

13th 

20th 

21st 

22d 

24th 

28th 

29th 

Death on the 29th. 



31,600 
31,000 
28,505 
44,000 
31,500 
40,000 
Sepsis began. 
5,661 • 
4,000 
3,400 
3,222 
800 
471 



93.6 
95.5 



92. 
94.7 



Zeissl's case, also of the lymphatic form, showed the following 



Date. 



White cells. 



Percentage of 
lymphocytes. 



September 9th . . . 

24th . . . 
26th... 
29th . . . 

October 6th 

9th 

" 10th 

" 11th 

" 12th. ..... 

" 13th. ..... 

" 14th 

" 15th, 

" 16th (A.M.) 
" 16th (P.M.) 



80,000 
113,000 
119,000 
122.000 
140,000 
Pneumonia began. 
119,000 

98,000 

68,500 

43,500 

50,000 
9,350 
133,200 
172,000 



97. 



88.7 
85.4 
75. 



Polymorphonuclear neutrophiles are absolutely as well as rela- 



1 15th Cong. f. innere Med., 1897. 
2 11th Cong. f. innere Med., 1893. 



LEUKEMIA. 



175 



tively diminished in most cases. Indeed they are often so scarce 
that one has to look through several thousand leucocytes before find- 
ing one. There is nothing abnormal about them — a point of marked 
contrast with the neutrophiles in myeloid leukaemia. Eosinophiles 
and myelocytes are equally rare. 

Summary. 

The leading characteristics of leuksemic blood are as follows : 
{a) Myeloid leukcemia. 

1. Eed cells about 3,000,000, nucleated forms very numerous. 

2. White cells about 450,000, of which 

3. Myelocytes form about thirty per cent. 

4. Every possible form of cell intermediate between the ordinary 
varieties is to be seen. ("Polymorphous blood.") 

(h) Chronic lymphatic leukcemia. 

1. Eed cells about 3,000,000 or lower; nucleated forms rare. 

2. White cells about 300,000, of which 

3. Small lymphocytes usually form over ninety per cent. 

4. Myelocytes and eosinophiles very scanty, 
(c) Acute lymphatic leukcemia. 

1. Eed cells much diminished; nucleated forms infrequent. 

2. Large forms of lymphocytes usually predominate ; many of 
them often show signs of degeneration. 

3. Neutrophiles and eosinophiles very scanty. 

Diagnostic Value. 

Leukaemia is distinguished by the blood examination from 

1. Hodgkin's disease: (a) splenic, {h) glandular. 

2. Tumors of the spleen and vicinity {e.g., kidney or retroperi- 
toneal glands). 

3. Enlargements of the lymphatic glands from tuberculosis, 
syphilis, malignant disease. 

4. Hydronephrosis. 

5. Huge leucocytosis from any cause. 

6. Chronic malaria. 

7. Amyloid disease. 

1. Leukcemia and Hodgkhi^ s disease (lymphadenoma or pseudo- 
leukaemia). The pathology of the two diseases is identical but for 
the blood count. In Hodgkin's disease the blood is normal, or 



176 



SPECIAL PATHOLOGY OF THE BLOOD. 



shows only a moderate anaemia or leucocytosis (polymorphonuclear 
cells alone increased), and the diagnosis is easily made. 

2. Tumors of the spleen and especially of the kidney are very apt 
to be mistaken for leukaemia. Within a single year I was asked to 
examine the blood in three cases of " leukaemia," all of which turned 
out to be malignant disease of the kidney. In all of these there was 
a large tumor resembling the spleen in the left hypochondrium, also 
a very large increase of white cells. In two of them the blood was 
examined fresh and the great number of white cells in the slide 
taken as evidence confirmatory of leukaemia. The stained speci- 
men, however, showed only marked leucocytosis with ninety per cent 
of polynuclear cells of the ordinary type and no myelocjrtes. Other 
large tumors of this region showed similar results. Occasionally 
cases of leuk;aemia with numerous metastases are described as " sar- 
comatosis," and then it is asserted that the blood of leukaemia is 
identical with that of sarcoma. The source of the mistake is ob- 
vious. 

3. Adenitis with hyperplasia due to tuberculosis shows usually 
normal blood ' and is thus easily distinguished from leukaemia. 
Leucocytosis is often present in syphilitic cases and still more 
marked in those due to cancer or sarcoma, but the counts rarely 
reach 30,000 and myelocytes are absent or very scanty. 

4. One case of hydronephrosis, in which the distention of 
the sac was so great that it presented as a hard, solid tumor 
on the right hypochondrium, was taken for leukaemia by a com- 
petent observer some years ago. The normal blood examination 
revealed the mistake, and excluded also malignant disease in 
all probability. The diagnosis was reached, however, only at the 
autopsy. 

5. Huge leucocytosis in pneumonia or malignant disease may 
cross the old boundary line of 100,000 white cells, beyond which 
none but leukaemic cases were supposed to venture. The differ- 
ential count sets us right instantly, showing ninety per cent or 
so of the increase to be made up of ordinary polymorphonuclear 
leucocytes. 

6 and 7. The large spleen and cachectic appearance associated 
with chronic malaria and long-standing suppurations may be easily 
distinguished from leukaemia by the absence of anything more than 
anaemia and leucocytosis in the blood. 

^ Sometimes marked leucopenia. 



LEUKEMIA. 



177 





Red cells. 


White cells. 


Lympho- 
cytes. 


Poly- 
nuclear 
leucocytes. 


Myelo- 
cytes. 


Nucleated 
red cells. 


Leukaemia (splenic- 




About 


450,000 ± 


About 7.6 


About 50 


About 37 


Very 


myelogenous) . 


3,000,000 


per cent. 


per cent. 


per cent. 


numerous. 


Leukaemia (1 y m - 


About - 


100,000 ± 


About 96 


About 3 


Absent. 


Rare. 


phatic). 


3,000,000 


per cent. 


per cent. 






Hodgkin's disease. . . . 


About 


7,500 ± 


Normal. 


Normal. 


Absent. 


Absent. 


normal. 










Tumors of or near the 


Usually 




Greatly 


Greatly 


Few if 


Few. 


spleen. 


diminished. 


40,000 ± 


decreased. 


increased. 


any. 




Leucocytosis in gen- 




May be over 


Greatly 


Greatly 


Few if 


Few 


eral. 




100,000 


decreased. 


increased. 


any. 


at times. 




Much 


Somewhat 


Usually 


Usually 


Few if 


Few. 




diminished. 


increased. 


increased. 


decreased. 


any. 




Amyloid disease 


Usually 


Usually 


Usually 


Usually 


Absent. 


May be a 


diminished. 


increased. 


decreased. 


increased. 




few. 


Hydronephrosis 


Normal. 


Normal. 


Normal or 


Normal. 


Absent. 


Absent. 






decreased. 









Effect of Intercurrent Infections. 

There are on record about thirty cases in which leukaemia (acute 
or chronic) has been complicated with some intercurrent infection, 
with marked effect upon the blood in all but one. This single case 
was an acute rheumatic arthritis reported by Richter in the discus- 
sion of Fraenkel' s article in the Deutsche medicinische Wochenschrift 
for 1895 (Nos. 39, 43, and 45), p. 639. Here the blood remained 
unchanged. 

Mtiller's' case of lymphatic leukaemia was complicated by a sep- 
ticaemia, and the count of white cells rose from 180,000 to 400,000 
per cubic millimetre, with a marked increase in the percentage of 
polymorphonuclear cells. Here was a genuine leucocytosis added 
to a leukaemia. 

With the exception of these two cases, all those hitherto pub- 
lished have shown a marked progressive decrease in the total num- 
ber of leucocytes without any change in the percentages of the 
different varieties' in twelve, while eight showed, like Mtiller's, an 
increased percentage of the polymorphonuclear cells despite the de- 
crease in the total leucocyte count. 

Marischler^ in a case of lymphatic leukaemia with cancer of the 
kidneys found: 

1. At First. 2. Later. 

Red cells 3,450,000 2.400,000 

White cells 96,000 48,000 

Haemoglobin 50 per cent 30 per cent 

'Mliller: Dent. Arcliiv fiir klin. Med., 1892, vol. 1.. p. 47. 
2 Wien. klin. Wocli., July 23d, 1896. ~ 

12 



178 



SPECIAL PATHOLOGY OF THE BLOOD. 



1. At First. 2. I^ter. 



Polymorphonuclear cells 

Small lymphocytes 

Large lymphocytes 

Eosinopliiles 

Myelocytes 



15.6 percent. 57.5 percent. 

83.3 " 40. 

1.8 " 1.6 
.18 " .16 



.16 



Various infections — miliary tuberculosis, pneumonia, grippe, 
erysipelas, abscess of kidney, septic lymph glands — alike decreased 
the leucocyte count. In one case a rise just before death was ob- 
served. 

Thus in Henck's case the leucocytes fell from 400,500 to 89,000, 
in one of Muller's from 246,900 to 57,300, in Kovacs' from 67,000 
to 17,000, in Zeissl's from 140,000 to 9,350. I have already men- 
tioned a case of lymphatic leukaemia (page 174) in which the leuco- 
cytes fell from 40,000 to under 500, this last being on the day of 
death. In this case the percentages of the different varieties of 
leucocytes remained entirely unchanged. 

Herrick ^ reports a case complicated by acute streptococcus in- 
fection in which the white cells w^ere 60,000 at the time of death. 
How high they may have been earlier is not known. 

It appears, therefore, that when an infection complicates leukae- 
mia we may have — 

1. No effect (see case of rheumatic fever as a complication, just 
mentioned) . 

2. A genuine leucocytosis on top, so to speak, of the leukaemia, 
with an increased percentage of polymorphonuclear cells. 

3. A decrease in the leucocyte count with or without an increase 
of polymorphonuclear cells. This decrease is by far the. most com- 
mon result and may go far below normal as death approaches. 

Goldschneider^ found that by the injection of splenic extract and 
other substances he could bring about a similaj' diminution in the 
number of leucocytes, but that, as in the case of intercurrent infec- 
tions, this diminution was not accompanied by any improvement in 
the patient's condition and death followed as usual. 

Abscesses occurring in leuksemic patients are filled with poly- 
nuclear leucocytes as ordinary abscesses are, and do not contain 
myelocytes. 



' Loc. cit. 

Discussion of Fraenkel's article. 



hodgkin's disease. 



179 



HODGKIN'S DISEASE. 

(^Pseudo-Leukceinia, Lymphoma). 

The diagnosis of this disease is impossible without the blood 
count. Its pathology is identical with that of leukaemia, and even 
post mortem the two diseases are indistinguishable so far as the 
lesions outside of the blood are concerned. Yet the blood is in no 
way peculiar, but presents in most cases all the characteristics of 
the normal tissue. Its value is as negative evidence, telling us in 
a given case that leukaemia is absent, even though all the other signs 
and symptoms may be those of leukaemia. 

(I.) Transitions from Hodgkin's disease to leukaemia are said to 
have taken place under the eyes of competent observers, but they 
are very rare. Only three such cases are on record so far as I know, 
that of Fleischer and Penzoldt,' that of Mosler,- and one reported 
by Senator,^ in which two sisters came under observation, both suf- 
fering from Hodgkin's disease. One died of it; in the ether the 
blood changed to that of leukaemia before death. ^ 

Doubtless many of the other cases supposed to exemplify a simi- 
lar transition were really cases in which a leucocytosis arose owing 
to some inflammatory complication, as not uncommonly occurs (see 
below, Table X.). 

From the existence of these very rare cases of a transition to 
leukaemia, it has been supposed, especially by French observers, that 
Hodgkin's disease is simply an early stage of true leukaemia, and 
that this would always become apparent were it not that the pa- 
tients die of some intercurrent disease before the signs of leukaemia 
have time to show themselves in the blood. One difficulty with this 
view is that there occur chronic cases which last from eight to ten 
years without any change in the blood. Another difficulty is that 
the transition is in fact rare, despite the relative frequency with 
which the disease is met with. 

(11.) Probably most cases diagnosed as Hodgkin's disease are 

'Deut. Arch. f. klin. Med., vol. xvii. 

^Ziemssen's "Handbucli d. Path, and Therap.," vol. viii. 

^Berl. klin. Woch., 1882, p. 588. 

■*It is noteworthy that all these cases are of some years' standing — before 
Ehrlich's methods were much used. Askanazy has more recently observed 
the transition in a case in which the blood was normal for two and a half 
years and then leukaemic for one and a half years under observation (quoted 
by Pinkus in NothnagePs "Specielle Path, and Therap.," vol. viii.). 



180 



SPECIAL PATHOLOGY OP THE BLOOD. 



in fact cases of glandular hypertrophy due to syphilis or tuberculo- 
sis, and this fact has led many to the belief that all cases called Hodg- 
kin's disease are in reality onl}^ syphilitic or tuberculous adenitis. 

'In a considerable number of cases, however, tuberculosis has 
been disproven by careful inoculation experiments with the glandu- 
lar tissue, and there is no reasonable doubt that soine cases at any 
rate are not due to tuberculosis or syphilis. Probably the diagnosis 
can never be made with absolute certainty during life. 

(III.) The frequent occurrence of fever and other symptoms 
characteristic of an infectious disease has led some writers to class 
it as such. In a certain percentage of cases the disease (like leukae- 
mia) has run an acute course, lasting not more than six weeks from 
the first symptoms to death. In some chronic cases the same sort 
of evidence of an infectious nature has been brought forward. Ul- 
cerations occur in the mouth and intestine, through which morbid 
products might gain admission. Various bacteria (pyogenic and 
others) have been found in the blood and tissues from time to time, 
but numerous negative examinations for micro-organisms are also on 
record, and the evidence is insufficient to establish the infectious na- 
ture of the disease. None the less, there is a growing tendency 
among the leading writers and observers in Germany and elsewhere, 
to believe that the disease will ultimately be shown to be tuberculous. 

(IV. ) Meantime most surgeons continue to regard it as a form of 
sarcoma' and to treat it like malignant disease. 

The Blood. 

Whatever the nature of the disease, we find in the earlier stages 
of most cases normal blood, as will be seen in Table X. (cases 7 to 
23 inclusive). 

As the disease progresses the haemoglobin soon begins to fall, 
later the red cells do so, until, as at the end of Case 10 of the present 
series, the blood may reach the severest grade of anaemia. In acute 
cases the anaemia may develop very rapidly. The usual qualitative 
changes characterizing severe secondary anaemia may be present. 

White Cells. 

When inflammation arises in the glandular tumors and some- 
times when none is found, the white cells may be greatly increased, 
even up to a ratio of 1 : 80 red cells, as in Case 1 of the present 

^ There are no rehable diflEerentla between sarcoma of lymph glands and 
"benign" lymphoma histologically. 



hodgkin's disease. 181 



Table X. — Hodgkin's Disease, 



No. 11 


Age. 


02 


Red 
cells. 


White 
cells. 


Per cent 
hsemo- 
globln. 


Remarks. 


1 


38 


F. 


5,500,000 


64,000 


75 


Polymorphonuclear cells, 95 per cent. 
Lymphocytes, 5 per cent. 


2 




M. 


3,848,000 


39,300 


48 


Acute. Diff.* 500. Polymorphonuclear cells, 
95.2 per cent. 
Lymphocytes, 4.6 per cent. 






3 


24 


F. 


4,886.000 


33,000 


53 




4 


19 


F. 


5,528,000 
5,160,000 


33,200 
25,400 




Diff. 300 cells. Polymorphonuclear cells, 86.5 
per cent. 

Six weeks later. Lymphocytes, 13.0 per cent. 
Eosinophiles, 1.5 






5 


19 


M. 


2,480,000 


20,200 


33 


Stained specimens normal. 


6 


36 






14,000 
21,200 


60 


June 6th. 






5,148,000 


50 


June 11th. Polynuclear, 93.8 per cent. 

Small lymphocytes, 3.6 per cent. 
Large lymphocytes, 3.0 " 
Eosinophiles, .3 
Myelocytes, .4 " 
No nucleated reds. Reds pale. Some 
few irregular in shape. 


7 


38 




4,312,000 


12,000 


42 


Polynuclear, 90.5 per cent. 
Lymphocytes, 7.5 
Eosinophiles, 2.0 " 




8 


59 






8,500 


68 












9 


38 


— 


3,760,000 


7,000 


65 




10 


34 




3,380,000 


6,800 
6,700 


40 


Polynuclear, 84.6 per cent. 
Small lymphocytes, 10.0 " 
Large lymphocytes, 3.3 " 
Eosinophiles, 1.4 " 
Myelocytes, .8 " 
Normoblasts = 1 
November 31st. T. 103°. 








3,512,000 


40 


Declm£^5th 1 ^^^^ ^^ain poorly. Fairly regu- 








6,300 
7,900 
7,600 


D^cember 8th I ^i^^' Tendency to d1- 








2,960,000 
2,828,000 


33 

38 


Declmbe? 9th' 1 minished size. Few large. 
SS£37th:J Slight poikilocytosis. 


11 


37 






6,200 










7,300 




February 19th. Count 300. 

Polynuclear, 89.0 per cent. 
Large lymphocytes, 3.0 
Small lymphocytes, 8.7 
Eosinophiles, .3 " 












12 


43 





3,880,000 


5,000 
3,800 


30 


January 6th. Count 500. 

Polynuclear, 57.6 per cent. 
Small lymphocytes, 29.9 
Large lymphocytes, 13.5 " 
Eosinophiles, .7 " 
Mast cells," .3 
Reds rather pale. Slightly irregu- 
lar in shape. 

January 13th. 
January 15th. 

January 31st. Polynuclear, 63.3 per cent. 

Small lymphocytes, 34.0 " 
Large lymphocytes, 3.8 
Eosinophiles, 0.0 " 
ISIegaloblasts = 1.0 
Normoblasts = 0.0 
Reds as before. 








3,650,000 


30 
30 








5,200 



* DifT.= Differential count of. 



182 SPECIAL PATHOLOGY OF THE BLOOD. 



Table X. — Hodgkin's Disease {Continued). 



Age. 


X 

a; 
c« 


Red 
cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 






3,252,000 
2,012,000 


3,000 

3,400 
5,000 


30 

30 
28 


February 8th. Polynuclear, 55.4 per cent. 
Large lymphocytes, 8.6 
Small lymphocytes, 36. " 
Eosinophiles, 0. " 
Reds as January 31st. 
February 13th. Polynuclear, 57.4 per cent. 

Small lymphocytes, 32.2 " 
Large lymphocytes, 6.4 " 
Eosinophiles, 4.0 " 
February 23d. Polynuclear, 70 per cent. 

Small lymphocytes, 26 " 
Large lymphocytes. 4 " 
Eosinophiles, 0 " 


44 




2,336,000 
2,140,000 


3,400 
4,000 


30 
35 


May 4th. Count 5(X) cells. 

Polynuclear, 82.0 per cent. 
Small lymphocytes, 15.6 " 
Large lymphocytes, 3.4 " 
Eosinophiles, 0.0 " 
No nucleated reds. Reds stain rather 
palely. Little variation in size. 
Slight irregularity in shape. 
May 28th. Polynuclear, 70 per cent. 
Small lymphocytes, 18 " 
Large lymphocytes, 12 " 
Eosinophiles, 0 " 
Reds similar to May 4th. 


38 










Polynuclear, 69 per cent. 
Lymphocytes, 26 " 
Eosinophiles, 5 " 










37 


M. 


5,990,000 


13,500 




Polymorphonuclear cells, 95 per cent. 
Lymphocytes, 5 " 


25 


M. 


5,440,000 


9,500 


59 


Death; autopsy. 


19 


F. 


5,724,000 


6,800 


42 


Polymorphonuclear cells, 50 per cent. 
Lymphocytes, 40 " 


Adult. 


M. 


3,652,000 


5,800 




Difl. 300. Polymorphonuclear cells, 50.0 per cent. 
Lymphocytes, 45.3 " 
Eosinophiles, 1.3 " 
Myelocytes, 1.7 *' 

Big spleen, pallor, nosebleed, debility. 


29 


M. 


5,210,000 
3,840,000 
1,000,000 


5,000^ 
5,600 




Two months later. 
Three weeks " 


58 


M. 


2,820,000 


4,800. 


60 


Polymorphonuclear cells, 80 per cent. 
Lymphocytes, 17 
Eosinophiles, 3 " 


21 


M. 


4,560,000 


4,000 
5,800 






23 


M., 


4,210,000 


3,332 




Myelocytes, 1 per cent. Big liver and spleen. 
Eosinophiles, 4 




M. 


3,800,000 


1,440 


67 


Diff. 500. Polymorphonuclear cells, 71.25 per cent. 
Lymphocytes, 28.00 
Eosinophiles, .75 " 
One normoblast. 








No 
leucocy- 
tosis. 




DilE. 200. Polymorphonuclear cells, 63.5 per cent. 
Lymphocytes, 36.5 " 
Eosinophiles, 1.0 " 

Many of the lymphocytes have two nuclei. 











hodgkin's disease. 183 



Table X. — Hodgkin's Disease {Continued). 



6 
52; 


Age, 


X 
OJ 
03 


Red 
cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


35 








No 




Diff. 300. Polymorphonuclear cells, 41.7 per cent. 
Lymphocytes, 48.4 
Eosinophiles, 9.3 
Myelocytes, .6 " 










leucocy- 
tosis. 




26 


4 


M. 




No 




Diff. 500. Polymorphonuclear cells, 60.2 per cent. 
Lymphocytes, 36.0 
Eosinophiles, 3.6 " 
Myelocytes, .2 " 
Two normoblasts. 








leucocy- 
tosis. 




37 




F. 








Diff. 500. Polymorphonuclear cells, 92.6 per cent. 
Lymphocytes, 5.2 " 
Myelocytes, 2.2 
No eosinophiles. 












38 








No 




Diff. 313. Polymorphonuclear cells, 62.3 per cent. 
Lymphocytes, 37.0 " 
Myelocytes, .6 " 










leucocy- 
tosls. 




29 


28 


M. 


5,218,000 


11,800 


85 


Polynuclear, 51 per cent. 
Small lymphocytes, 35 " 
Large " 7 
Eosinophiles, 7 " 


30 


30 


M. 


5,280,000 


6,800 


55 


Diff. Polymorphonuclear cells, 76.0 per cent. 
Lymphocytes, 22.3 
Eosinophiles, 1.4 " 
Myelocytes, .3 " 

No nucleated red cells. 


31 


32 


M. 


4,616,000 


2,400 


70 




32 








2,200 




Diff. Polymorphonuclear cells, 69 per cent. 
Small lymphocytes, 19 
Large " 18 " 
Eosinophiles, 4 " 

Few normoblasts. 











series. There is, however, no more resemblance to leuksemia than 
in any other form of leucocytosis, the polymorphonuclear cells alone 
being increased. There is no reason for supposing, as Reinert ' 
does, that relative diminution of the lymphocytes is owing to the dis- 
eased condition of the lymph glands, nor for believing with Pinkus 
(Nothnagel's " Specielle Path, and Ther.," vol. viii., 1901) that the 
relative increase of lymphocytes which some cases show is charac- 
teristic of Hodgkin's disease. Pfeiffer'-^ has recently reported a case 
of the cutaneous form of the disease with sixty per cent of lympho- 
cytes out of a total leucocyte count of 6,500. 

As in any other cachectic condition, small numbers of myelo- 
cytes may be found. They were seen in nine of our cases out of 
twenty-five in which a color analysis was made, the highest percent- 

^ " Die Zahhmg der Blutkorperchen," Berlin, 1891. 
'^Pfeiffer: Wien. klin. Woch., 1897. 



184 



SPECIAL PATHOLOGY OF THE BLOOD. 



age being two per cent. Eosinopliiles are usually decreased when 
leucoc^i:osis is present. 

Summary . • 
!N"ormal blood in early stages. 

Later often marked ansemia ; sometimes lencoc}*tosis. 

Diagnostic Value. 
The onh' help given us by the blood is in excluding leukaemia. 
Syphilis, tuberculosis, or malignant disease might cause similar 
blood changes or lack of changes. 

Effects or Splexectomy ox the Blood. 

Allien splenectomy is performed for abscess, hydatid, rupture of 
the spleen, or other local disease, it is followed, after a varying num- 
ber of weeks, by a hyperplasia of the lymph glands, associated with 
li/mjyJioci/fosis. How long this lympheemia lasts is not altogether 
clear. 

Later, after many months, a moderate eosinox^hilia may appear 
and the mast cells are increased. Ehrlich examined one case six 
months after operation in which a considerable lympheemia existed, 
the bulk of the lymj^hocytes being large. Eosinophiles were not in- 
creased. In another case he foimd the hmiphsemia persisting in the 
fifth year after operation, while the eosinophiles were between three 
and four per cent. Li two other cases he found (six and eighteen 
months after the operation) no hmiphocytosis. 

In the following table the records of four other cases are given : 



T-\BLE XI. 











O a5 




-S 

St = 












White 
cells. 


ifi 


f 


o5 


III 






Red cells. 














Remarks. 


X 




















ci 




















n 


4,570.000 
4,970,000 
5.180,000 
4,800,000 
4.353.000 
3.300.000 


8.000 
30.000 
65,000 
17.500 
11.700 
11.600 


63 
64 

i i 

66 

85 
85 


•■ 






■• 




Before operation. 
Thi'ee days after. 
Six days after. 
Forty-eight days after. 
Four Dionths after. 
Five vears after. 




3. "200. 000 


53.000 


65 












(1893,* for abscess.) Three 
weeks after. 



* Czerny : Cited in Laudenbacli : Arch, de Thysid., 1896, p. ','24:. 



hodgkin's disease. 185 



Table XI. {Continued). 











2 o 








o . 






Ked cells. 


White 
cells. 




c ^ & 
S'2 £ 


Small 

phocyt' 


Large 
phocyt 


inophil 




Remarks. 


i 

ca 
O 










% 




o 








4,500.000 


13,800 


80 












Four months after. 




1,634,000 


12,000 


45 


61 


16 


20 


3 


8.1« 


Operated (April 9tli,1893) 
















for malarial hyper- 
trophy with twisted 
pedicle. April 23d. 




2,460,000 


20,000 


87 


49 


18 


33 


1 




Mav 6th. 




4,530,000 


27,000 


110 


66 


18 


15 


1 


7.7;^ 


Mav 13th, 1894. 




3,977.000 


8,000 


100 


62 


21 


11 


6 


October 2d. 1895. 


f4 


4,850,000 


30,000 


108 


83 


8 


8 


1 




Operated for hypertro- 


















p li i e d , wandering- 
spleen. Before opera- 
tion. 




4,700,000 


39,000 


100 


91 


5 


4 


0 




Seven days after. 




3,630,000 


18,000 


105 


78 


15 


6 


1 




Two months after. 




2,750,000 


20,000 


• 63 


84 


5 


10 


1 




Three years after. 



+ Hartman and Vaquez : See. de Biol., February 5th, 1895. 



One point which these cases clearly prove is that no one A^ariety 
of leucocyte is supplied to the blood from, the spleen. 

Splenic Ax.^:mia. 
{Fseudo-Leukcemia Splenica^ Ancemia tvith Enlarged Spleen.^ 

I object to the term " splenic anaemia," because it seems to sug- 
gest that the splenic enlargement is in some way the cause of the 
anaemia, and for this there is no sufficient evidence. But, whatever 
term is used, there is at least one point about the blood of cases of 
idiopathic anaemia occurrmg in adults and associated w^ith enlarged 
spleen which deserves notice. This is the leucopenia. In Osier's 
article (^4?;?. Jour. Med. Sciences, January, 1900) the following 
counts are recorded: 



Case. 


Date. 


Red 
cells. 


White 
cells. 


C C c 

? ^ £ 
- 




^ ,1^ 
fiJ 


O (K C 

C £ 


Remarks. 


I. 


Feb. 1879. 


2,250,000 


7,100 










Recurring haeraatemesis and 
melsena. Death in an attack of 
melEena in 1897. 


IL 


1898. 


3,000,000 


2.800 


25 


84.4 


12.8 


2.8 


Hfematemesis for years at inter- 
vals. Splenectomy. Recovery, 



186 



SPECIAL PATHOLOGY OF THE BLOOD. 



q3 


Date. 


Red 
cells. 


White 
cells. 


ill 


Poly- 
nuclears, 
percent. 




O it's 
= 3i a; 

i '— r' 
^ — g_ 


Rennarks. 


III. 


1898. 


4,000,000 


6,500 


30 


73 


25 


9 
" 


Haematemesis and melaena fre- 

nil pn tl V 


IV. 


1895. 


4,816,000 


5,000 


55 










V. 


1896. 


3,600,000| 3,000 


66 1 66 


31 


1 




VI. 


1897. 


4,788,000 


5,200 


60 1 40 


59 


1 




VII. 


1898. 


4,128,000 


2,800 


45 








VIII. 


1898. 
Jan. 
June. 


3,328,000 
2,500,000 


2,000 
4,000 


40 
45 


78 


21.5 


.5 


Occasional normoblast. 


IX. 


1899. 


4,208.000 


4,000 


45 


65 


31.2 


3.3 




X. 


1899. 
Oct. 12th. 

" 17tii. 

Nov. 10th. 
" 20th. 


1,540,000 

1,380,000 

3,120,000 
3,680,000 


3,300 

3,250 

4.500 
4,300 


23 

20 

55 
54 


74 


23.8 


1.5 


Myelocytes, 1.5 per cent. While 

counting 300 leucocytes, saw 
\ Normoblasts, 32. 
'/ Megaloblasts, 13, 
While counting 400 white cells, 75 
nucleated reds were seen, 21 of 
which were normoblasts, 19 megal- 
oblasts, and 35 intermediate. 

No nucleated reds. 


XI. 


1899. 
Oct. 31st. 
Nov. 16th. 


3,a56,000 
3,992,000 


4,500 
3,500 


55 
60 


73.7 


25.3 


1 




XII. 


Nov. 18th, 
1899. 


4,270,000 


2,500 


45 


80.3 


14 


5 


Mast cells, 6 per cent. 



In eight of these twelve cases the leucocytes were markedly 
subnormal. In my own series (see following table) this abnormality 
is still more evident. 



Splenic An^ma. 





Age. 


Sex. 


Red cells. 


White cells. 


Hgemoglobin, 
per cent. 


Remarks. 


1 


24 




2,668,000 


15,800 


35 


Polynuclear, 62. per cent. 










Lymphocytes, 36. " 
Eosinopliiles, .4 " 
Myelocytes, 1.2 " 
Basophil es, 4. 


2 


12 




2,268,000 


9,800 


25 


With neck glands. 










Polynuclear, 74. per cent. 
Lymphocytes, 25. " 
]\Iyelocytes, 1. " 
Normoblasts, =4. (Count 
500.) 








3,320,000 




22 


20 days later. 








3,336,000 




25 


56 " 



hokgkin's disease. 

Splenic Anemia. — Continued. 



187 



Age. 



Sex. 



Ked cells. 



White cells. 



Haemoglobin, 
per cent. 



Remarks, 



13 



18 



45 



17 



4,280,000 



2,224,000 
384,000 



4,024,000 
3,048,000 

2,560,000 



2,456,000 
4,912,000 



2,100 



1,300 
6,400 

1,800 



1,900 
1,450 
1,500 
1,600 



700 
650 



1,700 
900 

2i2()6 
1,400 



42 



48 
30 

35 



45 
35 

35 



20 



45 
40 
50 



Polynuclear, 59. per cent. 
Lymphocj^tes, 40. " 
Eosinopbiles, 1. " 
No nucleated reds. 
7 days later. 

15 " dying of hemor- 
rhage. 

Polynuclear, 55. per cent. 
Lymphocytes, 37. 5 " 
Eosinophlles, 7.5 " . 
No nucleated reds. 
8th day. 
12th day. 
15th day. 

Polynuclear, 44. per cent. 
Lymphocytes, 55. " 
Eosinophiles, 1. " 
Two normoblasts. (Count 

500 cells.) 
July 21st. 

Repeated. Polynuclear, 66^. 
Lymphocytes, 33. per cent. 
Eosinophiles, 1. " 
(No nucleated in 150.) 
July 27th. 
July 31st. 
August 11th. 
August 20th. 

November 18th. Following 
July 5th, doing well. 



PART II. 

ACUTE INFECTIOUS DISEASES. 



CHAPTER III. 

INFLUENCE OF FEVER ON THE BLOOD. 

Some of tlie blood changes found in acute infections are to be 
regarded as due simply to tlie fever associated with the disease. It 
is worth while, therefore, to consider what fever per se can do to 
the blood. 

Maragliano^ and others haA^e shown that during fever from any 
cause a contraction of the peripheral vessels occurs. When fever 
disappears, whether spontaneously or from the action of antipy- 
retics (phenacetin, quinine, etc.), a dilatation the vessels follows. 

Following the laws to which we have so often alluded, the con- 
traction of the vessels causes a concentration of the blood with rise 
in specific gravity and in the number of blood cells per cubic milli- 
metre. This concentration is still further increased by the greater 
loss of water which the organism suffers during fever than under 
normal conditions. 

The effect of these two influences in increasing the number of 
red cells per cubic millimetre is, however, counteracted to a con- 
siderable extent by the sharing of the blood in the general tissue 
destruction which goes on with increased rapidity during fever. 
Many corpuscles are thus destroyed, but until the temperature falls 
the anaemia is covered up by the concentration. AMien the fever 
leaves the patient there is a sharp fall in the number of cells per 
cubic millimetre, due partly to the destruction of corpuscles (hither- 
to masked by concentration) and partly to the dilution of the blood 
which is the result of the post-febrile dilatation of the peripheral 
vessels above mentioned. The suddenness of this fall in the count 
is proportional to the suddenness of the fall in temperature. 

The alkalinity of the blood has been often said to be diminished 
^ Zeit. f. klin. Med., vols. xiv. and x\u. 



PNEUMONIA. 



189 



in fever, but recent research tends to show that these results were 
obtained by faulty technique, and it is doubtful whether the re- 
action of the blood shows any constant changes in fever. 

Leucocytes and fibrin show no constant changes, though in the 
majority of infectious fevers they are increased. 

P^nTEUMONIA. 
The Blood as a Whole. 

(a) Bacteriology. — The diplococcus lanceolatus has been found 
in the blood of pneumonic patients repeatedly, especially in those in 
whom there has been some secondary diplococcus infection {e.g., 
diplococcus endocarditis) ; but such findings are rare and have gen- 
erally been in fatal cases with very severe generalized infection. 

For example, Sittmann^ out of 16 cases found diplococei in the 
blood of 6, most of which were complicated with lesions in other 
organs, and 4 of which were fatal, while of the 10 whose blood was 
sterile, 9 ended in recovery. 

Eoulay'^ found the organism in 2 cases shortly before death. 
Belf anti ^ found it but 6 times out of a large number of cases, and 
of these 6, 5 were fatal. Goldschneider^ and Grawitz^ got similar 
results . Cohn® in 32 cases found the organism in 9 ; 7 of these 
were fatal. The other 2 had empyema and other evidences of 
metastatic action of the pneumococci. Beco' studied 49 cases. 
Twenty of these ended fatally, and of these 20 there were 5 whose 
blood showed pneumococci by culture and 1 from which Friedlan- 
der's bacillus was cultivated. Out of 29 cases ending in recovery 
only 2 showed cocci in cultures from the blood. If large numbers 
of colonies can be cultivated from the peripheral blood, Beco con- 
siders the prognosis grave. A few colonies, however, are of no 
significance in prognosis. Fraenkel has obtained over 300 colonies 
from one puncture. Their virulence was less than that of those in 
the sputa, showing apparently the effects of the blood's antitoxic 
power. Nevertheless, it is obvious that the presence of pneumococci 
in the blood is a bad prognostic sign. 

'Deut. Archiv f. kiln. Med., 1894, p. 323. 
Paris Thesis, 1891. 
3 Riforma Medica, Naples, 1890, No. 37. 
■^Deut. med. Woch., 1892, No. 14 
5 Grawitz : Charite-Annalen, vol. xix. 
«Cohn: Deut. med. Woch., 1897, No. 9. 
^Beco: Revue de Med., 1899, July 10th. 



190 



SPECIAL PATHOLOGY OF THE BLOOD. 



(b) Coagulation is remarkably rapid, and in fresh specimens the 
fibrin network is very thick and appears within a few minutes, ex- 
cept in the rare cases with subnormal leucoc^-tes. Here it may be 
absent or diminished. 

(c) In cases Avith cyanosis the blood is often concentrated at the 
periphery so that its specific gravity is high and the number of cor- 
puscles large. 

(// ) Monti and Berggriin' observed that in children the specific 
gravity was high throughout the course of the disease, falling with 
the temperature. 

The toxicity of the blood is doubled (Albu : Virchow's Archiv. 
vol. 149). 

Bed Ctlls. 

During the fever the red cells are approximately normal (unless 
increased by cyanosis") ; but after the crisis there is often slight 
anaemia, and sometimes a severe one. The haemoglobin is more 
markedly and more lastingly reduced than the number of red cells. 

A more interesting and important observation was made by Tiirck 
in 189S. viz.. that when the infection is severe or the patient of 
low vitality nucleated red cells (mostly normoblasts) may appear in 
the peripheral blood. In all Tiirck" s cases megaloblasts as well as 
normoblasts occurred, but the latter were greatly in the majority. 
Dr. Badger and I studied a most interesting case of this type in 
1898. The pneumonia ran a severe course and was followed by an 
empyema Avhich proved fatal. The blood counts were made for the 
most part after the crisis. At autopsy the marrow of the femur 
was bright red from end to end. The blood shoM-ed the following: 



Date. 


Red 
cells. 


White 
cells. 




2 - 






^ ~ "z 


«^ a: 

zi - 




— -r. 
|| 


1898- 

Januarr loth 






4-5 
















14th 




:1.5m 


90.6 


' 7.6 




■3.0 


'600 


22 


'4 


loth 








S4.5 


S n 




7.0 


600 




15 


Vy.h 








>4.5 


12. >i 


n.2 


3.5 


600 


54 


4 


ITrh 










n.l 




6.5 


700 


24 


3 


l>t:l 










10.11 




2.5 


500 


? 




19l:i 




ii^TCX'i 












2»:irh 




2o.C>00 


•• 


■^"..5 


7.5 






■406 


"3 




21^t 




24.CKX) 




92.0 


7.ti 




0.3 


300 


3 


'i 


22d 






s:.o 


12.5 


0^ 




400 




24th 












2<3th 




19. im 



















Many of Turck's stimtilation forms and many netitrophiles intermediate between myelo- 
cytes and polynuclear cells were seen. 

^ Arch. f. Kinderheilk.. vol. xvii. 



PNEUMONIA. 



191 



Maragliano has noticed degenerative changes in the red cells 
in severe cases. 

WJiite Corpuscles. 

1. Probably as early as the time of the chill, and certainly within 
a few hours after it, the leucocytes are greatly increased, and usu- 
ally continue so throughout the febrile period. 

2. There is no correspondence between the daily variations in 
temperature and the leucocyte curve. In cases in which a pseudo- 
crisis occurs (the temperature falling but rising again), the leuco- 
cyte count usually remains high, while at the time of the true crisis 
and often a few hours before it the leucocytes begin to fall. This 
fall, however, is hardly ever by "crisis," but though starting per- 
haps a little before the temperature it is one to two days longer in 
reaching normal. When the temperature reaches normal by lysis 
the leucocytes fall with it, but generally more slowly, and reach 
normal later. 

3. When resolution is delayed the leucocytosis continues, some- 
times for weeks, and very gradually falls to normal in cases in 
which resolution eventually occurs without complication. If ab- 
scess, empyema, or gangrene follow, the leucocytes usually become 
still further increased. 

4. The degree of leucori/tosis is probably the resultant of the fac- 
tors mentioned on page 105, and does not run parallel to the degree 
of fever or the amount of lung involved. Xevertheless, cases with 
extensive signs in both lungs, and especially those complicated by 
empyema or other suppuration, are more apt to have very high 
counts, provided the " reaction " of the patient against the infection 
is vigorous. Children have especially high count as a rule (see ex- 
ception below). The cases appear to fall into the following groups 
as regards the degree of leucoc}i;osis present. 

1. Mild infection, vigorous reaction = sliglit leucocytosis. 

2. Severe or moderate infection, vigorous reaction = marked 

leucocytosis. 

3. Severe infection, feeble reaction = no leucocytosis. 

{a) The patients in Class 1 all recover, but they are very few in 
number, (b) Those in Class 2, which includes over nine-tenths of 
all cases, may or may not recover, according as the fight between 
patient and disease comes out one way or the other. 

(c) Those in Class 3 almost invariably die ; there is not safl&cient 
of a struggle to raise the leucocyte count. A striking exception to 



192 



SPECIAL PATHOLOGY OF THE BLOOD. 



this rule is reported by Stockton [Phil. Med. Jour., June 25th, 1898), 
a case of lobar pneumonia in a child of eight with three relapses and 
a total course of sixty-eight days. At the height of the second 
relapse the blood was examined and showed only 4,000 leucocytes 
per cubic millimetre. Of these there were forty-four per cent of 
polymorphonuclear, fifty per cent small lymphocytes, six per cent 
large lymphocytes. In the second apyretic interval, sixteen days 
after the first examination, the count stood 7,840 leucocytes per cubic 
millimetre. Of these thirty-four per cent were polymorphonuclear, 
sixty per cent small lymphocytes, and twenty per cent eosinophiles, 
four per cent large lymphocytes (?). 

After the third seizure (three weeks later) the leucocytes were 
10,080, with polymorphonuclear forty-five per cent. Small lympho- 
cytes forty-six per cent, eosinophiles eight per cent, large lympho- 
cytes one per cent. 

On the sixty-eighth • day (in convalescence) the blood showed : 
Eed cells, 4,952,000; white cells, 7,600; haemoglobin, 90 per cent. 
Polymorphonuclear, 57 ; small lymphocytes, 36 ; large lymphocytes, 
2.5; eosinophiles, 4.5. 

Very possibly this infection may have been due to some other 
organism than the diplococcus lanceolatus. 

When either the patient or his disease easily gains the mastery 
there is no leucocytosis, or a very slight one ; but in the much larger 
class of cases in which the struggle is a fierce one, leucocytosis ap- 
pears, tvhichever ivay the struggle results. 

Pick ' noted that pneumonia complicating smallpox when the 
patients were already very sick, caused no leucocytosis, and the same 
is often true in those whose power of resistance is reduced by age, 
alcoholism, typhoid, or by some chronic disease. 

Von Jaksch, noticing the fatality of cases without leucocytosis, 
suggested that we should induce leucocytosis by injecting turpentine 
or other irritants so as to cause abscess ; but this has not proved of 
any benefit to the patient, nor has the production of leucocytosis 
without abscess, as can be done with pilocarpine or nuclein, been 
any more successful. There is no difficulty in producing the leu- 
cocytosis by these means, but all observers are agreed that it does 
the patients no good. 

Leucocytosis is checked by antipyretics (Hare^) but not by cold 

^ Arch. f. Dermat. und Syph., vol. xxv., p. 63. 
2 New York Medical Record, May 9th, 1896. 



PNEUMONIA. 



193 



bathing, which speaks in favor of the latter method of reducing 
temperature. 

The general course of the leucocytes is seen in the accompanying 
charts from Billings, to whose excellent article I am greatly in- 
debted. 

Chart I. — Pneumomia, Showing Fall by Crisis (Billings). 

Feb. \ 16 \ 17 \ 18 \ 19 \ SO \ SI \ S3 \ 



a ^ m i 




2 ( 




' 1 








2 


5 




? r 




5 m 6 izi 


5 tn 


S ' 


? 


F m ( 


f * 


106° 




















































































































105° 




















































































































10^ 




















































































































103° 












































































t 








































102° 














, f 


























































\l 






V 






































101° 














it 






































































































100° 




















































































































99° 




























4- 






























98" 
























L 






















































































— • 




























































S0.O0O 

ao,ot»0 
18,000 
)S.0OO 
UvOOO 

u.ooo 

10,000 • 
fi.000 

J5;000_ 










































































































































































































































































































































































































































































































































































































































































































































































































































\ 








































































































































































































































































































































































































































3,000 


















































































































1 























































The upper chart shows the course of the temperature, the lower that of the 

leucocytes. 

Qualitative Changes. — As inmost forms of leucocytosis, the poly- 
morphonuclear leucocytes are enormously increased both absolutely 
and relatively, often making over ' ninety per cent of all the white 
cells. Eosinophiles and blood plates disappear and the lympho- 
cytes are absolutely and relatively much reduced. After the crisis 
13 



194 



SPECIAL PATHOLOGY OF THE BLOOD. 



this is reversed, the polymorphonuclear forms falling often below 
sixty per cent, while the eosinophiles and blood plates are above 
normal. The return of the eosinophiles to the circulation often 
occurs a day or two before the crisis. It seems to mean that the 
acme of the process has passed, and so constitutes a favorable sign in 

Chart II. — Pneumonia and Rheumatism. 

May. Jxme. 



24 


L 2 


; St 


; 27 s 


9 99 3 


y 5/ . 2 




4- 5 i 




fOG° 




















































































































105° 




















































































































104° 


























































103° 


—r 

-i- 
















































































































lOZ" 


















































































































10 


































































\ 
















































100° 
















































































































f- 


99° 










































































































































































98° 


























































97° 


















































































































80,000 

S0,000 
18,000 
16,000 
14,000 
W,000 
10.000 
8,000 
__6^ 0 _ 

4,000 
8,000 














































































































































i 


-C- 






















































< 
























































-e 

:> 






























I 




























































\ 














































































K 










\ 


















i 








% 
































\ 


























































\ 
































/ 





































































































































































































































































































































































The upper chart shows the course of the temperature, the lower that of tlie 

leucocytes. 

most cases. After the crisis the eosinophiles may run up to five to 
six per cent (300-450 absolute). 

Myelocytes maybe abundant (11.9 per cent or 1,056 absolute) 
and stimulation forms and transitional neutrophiles numerous. 
They have no known prognostic significance. 

At and just after the crisis a great increase of blood plates takes 
place, gradually disappearing lat^r. 

As to the differential count in the (fatal) cases in which leuco,- 
cytosis is absent, data are scanty. Bieganski thought the polymor- 



PNEUMONIA. 



195 



phonuclear varieties decreased, Kieder found them increased, while 
Billings finds them normal. Xo general law can be stated on this 
point as yet. 

In a case of bronchopneumonia complicating pertussis studied 
at the Mass. General Hospital in 1894, the conditions were entirely 
different from those just stated. The patient, a girl of six, had at 
entrance 72,100 leucocytes per cubic millimetre. Two days after 
the count was 91,600. A differential count made at the same time 
sliowed that the small lymphocytes made up 66 per cent of all the 
91,600 leucocytes per cubic millimetre. The polymorphonuclear 
cells were reduced to 30 per cent. Lymphatic leukaemia was thought 
of, but the leucocytosis was gone in ten days, and within a fortnight 
the patient left the hospital well. In the light of recent studies in 
pertussis this is now explicable (see below, p. 218).' 

Diagnostic and Prognostic Value. 

1. In cases of so-called " central imeumonia, " in which the symp- 
toms but not the physical signs of the disease are manifest, the pres- 
ence of a well-marked leucocytosis is often of great diagnostic value. 
It excludes malaria, typhoid, and uncomplicated grippe as causes of 
fever, and if scarlet fever and suppuration can be excluded by other 
evidence, it makes pneumonia very probable. 

I have repeatedly seen the diagnosis of pneumonia made in the 
absence of physical signs and largely on the evidence of the blood 
count, the diagnosis being confirmed several days later by the ap- 
pearance of typical signs of consolidation. In a patient of Dr. F. C. 
Shattuck's, sick five days, yet showing no signs of consolidation of 
the lung, the presence of a marked leucocytosis excluded typhoid, 
the only other likely diagnosis, and led Dr. Shattuck to treat the 
case as pneumonia, the wisdom of which course was later demon- 
strated by the appearance of signs of consolidation. 

2. Between pneumonia and capillary bronchitis the condition of 
the blood is of no help, as the latter also causes leucocytosis, and 
some cases affecting the larger tubes do the same. 

3. In cases of pneumonia occurring in very old or very young peo- 
ple, in which the fever and symptoms may be very slight, the pres- 
ence of leucocytosis may be the first thing to direct our attention to 
the lungs, dyspnoea and cough being absent. 

' Stienon: Jour, de Med., de Chirurg. et de Pharm., Bruxelles, 1895, t. iv., 
fasc. 1. 



196 



SPECIAL PATHOLOGY OF THE BLOOD. 



In prognosis, tlie important point is that the absence of leucocyto- 
sis is a very had sign, ichile its presence is neither good nor had. It 
must be remembered also that in the very mildest cases we may 
find the same absence of leucocytosis which in any other but the 
mildest would be almost surely fatal. 

This last point, which appears to me of great importance, is 
illustrated by the following figures : 

Halla reported 14 cases ; 2 had no leucocytosis, and both were 
fatal. 

Billings reported 22 cases ; 1 had no leucocytosis and was fatal. 

Laehr with 16 cases, and Kieder with 26, got similar results. 

Ewing in 101 cases found leucocytosis absent in 6 ; 6 were fatal. 

Von Jaksch and Kilodse likewise maintain that the absence of 
leucocytosis is usually fatal. 

In the Massachusetts General Hospital 566 cases have been 
studied. In general they entirely confirm the results obtained by 
BilliQgs and summarized above : 62 of them presented no leucocyto- 
sis at any time, and of these 50 were fatal, another one seemed 
moribund but finally recovered. 

The evidence, therefore, is in favor of the view that when leu- 
cocytosis is persistently absent in any but the mildest cases the 
prognosis is almost fatal. The presence of leucocytosis, on the other 
hand, is no guaranty ivhatever of a favorable issue. 

Reappearance of eosinophiles is a favorable sign in most cases. 

The series of cases at the Massachusetts Hospital is too large to 
exhibit in tabular form. Their results may be summarized as fol- 
lows : 

Cases with leucocytes under 10,000 = 62 (50 of these fatal) 





between 


10,000 


to 


15,000== 82 






15,000 




20,000 = 138 




u 


20,000 




25.000 = 121 






25,000 


u 


30,000= 76 






30,000 




35,000= 32 






35,000 




40,000= 21 






40,000 




45,000= 16 






45,000 


ii 


50,000= 7 


(( 


(C 


50,000 


il 


55,000= 7 




;c 


55,000 




60,000= 1 


(( 


u 


60,000 


ii 


65,000= 1 




(( 


65,000 




70,000 = 1 


u. 


» 


100,000 


il 


110,000= 1 










566 



TYPHOID FEVER. 



197 



Broncho- Pneumonia. 

In forty -nine cases of broncho-pneumonia recorded at the Massa- 
3husetts General Hospital, the following counts are recorded. 

Counts. 

8 
13 
22 
22 
4 
5 
1 
2 
2 
1 

3 (same case) 
83 

The highest counts in this series were in a case of broncho-pneu- 
monia in a baby of fifteen months. As the lymphocytes made up 
the larger part of the increase, and as the cough came in paroxysms 
with great cyanosis, pertussis was suspected. This case has already 
been referred to on page 114, and a similar case is recorded on page 
195. 

TYPHOID FEVER. 

Bacteriology of tlie Blood. 

Although it has long been known that the bacilli of Eberth could 
occasionally be found in the circulating blood or in the rose spots of 
typhoid cases, yet it is only within the last few years that such find- 
ings have been sufficiently constant to be of any practical value in 
diagnosis. 

Klihnau using 5-10 c.c. of blood found typhoid bacilli in two out 
of four cases. 

Neufelt {Zeit. fitr Hygiene, xxx., 3, p. 499) acted upon the belief 
that typhoid bacilli find . lodgment in the skin, protected from the 
destructive agencies which ordinarily destroy them in the circulating 
blood. In the skin the bacilli produce the rose spot. In the at- 
tempt to cut out a rose spot for the purpose of cultivating the ba- 
cilli, the blood which flows from the cut must be instantly diluted, 
else it will kill off the now exposed bacilli on the spot. 

By excising several spots, Neufelt succeeded in cultivating the 



Between 5,000 and 


10,000 


10,000 " 


15,000 


15,000 " 


20,000 


20,000 " 


25,000 


25,000 " 


30,000 


30,000 " 


35,000 


35,000 " 


40,000 


40,000 " 


45,000 


45,000 " 


50,000 


50,000 " 


55,000: 


" 100,000 " 


185,000 : 



198 



SPECIAL PATHOLOGY OF THE BLOOD. 



bacilli in thirteen out of fourteen cases of typhoid fever. The re- 
sults often gave proof of the nature of the disease before the Widal 
reaction had appeared. Curschmann (JMundi . med. Wocli . , Novem- 
ber 28, 1899), using not over two spots in each case, but following 
in other respects Neufelt's technique, got positive results in fourteen 
cases out of twenty. 

Richardson (Phil. 3Ied. Journal, March 3, 1900) got positive re- 
sults in five cases out of six. 

Q 1 1 an tit a ti i ' e Ch anges . 

1. The blood 2)lates are usually scanty, and the amount of fibrin is 
dimmished. In one of Tlirck's cases, blood plates and fibrin were 
nearly absent, and a hemorrliagic diathesis developed. He considers 
a rapid falling off of the amount of fibrin and blood plates a bad 
prognostic sign, but in a case of hemorrhagic typhoid reported by 
Hamburger (Johns Hopkins Hospital Eeport, vol. viii.) recovery 
took place although the coagulation time was ten minutes. 

2. Specific gravity follows the course of the haemoglobin. 

3. The general effects of fever (see above, page 188) are in part 
accountable for the changes next to be described, while some of 
them are more peculiar to typhoid fever. 

Red Cells. 

In Thayer's admirable study (Johns Hopkins Hospital Eeports, 
vol. viii.) we find the following analysis of two hundred and sixty- 
five counts. 

Weekly Average Based on One Count Per Week in Each Case, the 
Average Being Tai^en for the Week in Every Case in Which 
Multiple Counts Were Made. 



1st week 32 counts 4,913,312 

2d " 83 " 4.706,855 

3d " 54 " 4,555,814 

4tli " 34 " 4,187,720 

5tb " 22 " 4,118,590 

6th " 87 " 4,028,428 

7tli " 8 " 3,309,125 

8th " 8 " 3,652,285 

9tli " 6 " 3,509,666 

10th " 1 count 3,920,000 

lltli " 1 " 2,109,333 



All these counts refer to the febrile period of the disease. 



TYPHOID FEVER. 



199 



Eighty counts were made during convalescence. The results were 
as follows : 

Estimates of the Red Blood Corpuscles During Convalescence, 
Arranged According to the Period after the Last Day of Fever. 



1st week, 32 counts 4,540,000 

2d " 22 " 4,637,100 

3d " 15 " 4,252,000 

4th " 6 " 4,391,000 

5th " 2 " 5,469,000 



Thayer comments : " It will be noticed that in the first week (of 
fever) the number of red blood corpuscles is already somewhat below 
the normal " — that is taking the normal as from 5,500,000 to 6,000,- 
000, as it seems proper to do in this country (see page 56). 

From this point it steadily sinks week by week for the first nine 
weeks. After that the number of counts is too small to justify 
conclusions. The lowest point is probably reached about the end of 
defervescence in the majority of uncomplicated cases, yet when defer- 
vescence is slow, blood regeneration may begin well before the end 
of the febrile period. In the first two weeks of convalescence, re- 
generation is going on slowly. After the second week, in addition 
to the fact that the estimates are but few, the results are vitiated by 
the fact that the cases remaining in the hospital at so late a period 
were for the most part instances of severe fever of long duration, 
after which, as is shown by the first table, a much greater degree of 
angemia is reached " (Thayer) . 

Showing the Highest and Lowest Counts in Each Week. 



Highest. Lowest. 

1st week 6,940,000 3,400,000 

2d " 6,604,000 2,240,000 

3d " 6,916,000 2,300.000 

4tli " 5,884,000 1,426.000 

5th " 6,312,000 1,352,000 

6tli " 4,904,000 2,014,000 

Ttli " 4,500.000 1,648,666 



In only one of these cases could the high count be explained as 
a concentration of the blood through diarrhoea and vomiting, but 
counts made just after a bath are often very high owing to blood 
concentration.^ 

^ Antipyrin and acetanilid have no effect on the red cells. 



200 



SPECIAL PATHOLOGY OF THE BLOOD. 



Hcemoglohin. 
Thayer's figures are as follows: 



1st week of fever, 21 estimates average 76 per cent. 

2d " " 50 " " 73 

3d " " 32 " " 67 

4tli " " 20 " " 60 

5tli " " 15 " " 58 

6tli " " 6 " " 62 

7tli " 4 " " 50 

Convalescence 1st week, 22 estimates average 67 per cent. 

2d " 19 " " 69 

3d 12 " " 67 



This table shows a gradual decline during the febrile period, with 
a very slow regeneration in convalescence. The haemoglobin (as in 
most secondary anaemias) suffers more than the count of corpuscles, 
and is slower in reaching the normal, so that the color mdex is low 
throughout (see chart on p. 202). 

Leucocytes. 

Thayer records 832 estimates of the white cells in uncomplicated 
cases. 

Based on one count per week in each case, the average being taken for the 
week in every case in which multiple counts were made. 



1st v^^eek of fever, 100 counts 6,400 

2d " " 206 " 6,200 

3d " " 150 " 5,700 

4th " 95 " 5,400 

5th " 58 " 5,380 

6th " " 19 " 5,800 

7th " 13 ^' 6,300 

8th " " 12 " 6,400 



Thayer comments : " It would seem that the longer the disease 
lasts, the more profound the prostration, the lower the count." 
Ewing says : " The more severe the typhoid intoxication the lower 
the count. " How great the variations may be even in the absence 
of any apparent complication is shown in the following table : 

Highest. Lowest. 

1st week of fever 15,000 1.600 

2d " 18.000 1,000 

3d " " 13,000 1,000 

4th " " 10,500 1,700 



TYPHOID FEVER. 



201 



Highest. Lowest. 

5tli week of fever 10,500 2,300 



6th " " 10,000 3,250 

7tli " " 11,000 4,000 

8tli " " 9,250 4,000 

9th " " 9,300 2,000 



Most of these high, counts were in the blood of one individual, 
who, throughout the disease, without any apparent reason, showed 
constantly a large number of colorless corpuscles. The count of 
18,000 may have been after a cold bath, which Thayer has pre- 
viously shown often raises the count of white cells. 

In convalescence the count of leucocytes begins to rise toward 
the normal as the following table indicates : 



1st week of apyrexia, 32 counts 6,000 

2d " " 24 " 6,700 

3d " " 16 " 6,300 

4th " " 6 " 7,570 



Thayer's results may be exhibited in the following chart (page 
202). 

In the majority of the one thousand cases recorded at the Massa- 
chusetts General Hospital, the course of the leucocytes from w^eek 
to week has unfortunately not been followed with accuracy. 

Most of our counts were made on the day of entrance to the 
hospital, presumably during the first or second week of the fever. 

The range of the counts was as follows : 



Between 


1,000 and 


2,000 = 


10 cases. 




2,000 " 


3,000 = 


56 " 




3,000 " 


4,000 = 


135 " 




4,000 " 


5,000 = 


187 " 


u 


5,000 " 


6,000 = 


156 " 


. u 


6,000 " 


7,000 = 


149 " 


u 


7,000 " 


8,000 = 


112 " 




8,000 " 


9,000 = 


78 " 




9,000 " 


10,000 = 


60 " 




10,000 " 


11,000 = 


27 " 


ii 


11,000 " 


12,000 = 


19 " 




12,000 " 


13,000 = 


6 " 




13,000 " 


14,000 = 


3 " 


ii 


14,000 " 


15,000 


2 " 



1,000 cases. 

From these figures I have excluded all cases counted only under 
circumstances likely to concentrate the blood (cyanosis, after baths, 
after severe diarrhoea). 



202 



SPECIAL PATHOLOGY OF THE BLOOD. 



Of these cases 970 or 97 percent had less than 11,000 leucocytes 
per cubic millimetre at the time of entering the hospital, and 69.3 per 
cent had less than 7,000. 

Chart of the Blood in Typhoid Fever. 
Febrile period — weeks Convalescence— weeks. 



/ J? 3 ^ S ^ if f / 



































































































































































































































































































































































































/ 






















































































••• 






































































/ 















































































































































































































t 




























































































































































































































>- 








































































^^^^ , 







































Plain line = red cells. Dotted line = haecioglobin. Broken line = white cells. 

But these figures, like those reported by Thayer and Ttirck, differ 
from the reports of some other observers in not showing so large a 



TYPHOID FEVER. 



203 



proportion of very low counts. Thus Khetajurow expects to find 
only 2,500 to 3,000 leucocytes in the third and fourth weeks, but 
our observations show that this is not a law. 

Complications. 

Thayer's study of the effects of complications is by far the most 
thorough ever published, 

1. HeiiLori'liagafroni tlie Boivels (11 cases ). The red cells fall off 
markedly in one case from 3,648,000 (eighteen days before) to 1,992,- 
000, in another to 2,000,000 ; yet the first of these cases recovered. 

The leucocytes showed no appreciable change in half of these 
cases, while in the rest there was some leucocytosis (24,800 in one 
case, 17,400 in another, 10,500 in a third), reaching its maximum 
in from twelve to twenty-four hours, and returning to normal in 
from two to seven days. 

2. F erf oration of the Boivel (8 cases). Leucocytosis was well 
marked in three (16,400, 23,400, and 16,000), slight in two (10,400 
and 11,200), and completely absent in three, at the time of the per- 
foration. Thayer studied the clinical features of these cases and the 
results of cultures made at operation, and concludes : " It is probable 
that slight local peritonitis always produces . . . leucocytosis unless 
the individual is already in a condition of profound general septi- 
caemia. On the other hand, a sudden (general) infection of the 
peritoneum with large quantities of excessively malignant organ- 
isms may often result in complete absence of leucocytosis or a rela- 
tively slight rise, followed later by a fall. Three cases of strepto- 
coccus peritonitis showed no leucocytosis at anytime. The prospect 
of relief by surgical interference is best in those cases with a leuco- 
cytosis." Thayer also shows that a preperforative leucocytosis due 
to local peritonitis about deep ulcers may occur. He adds, how- 
ever, a summary of four cases in which symptoms suggesting per- 
foration and accompanied by leucocytosis led to a laparotomy, yet 
in which no perforation was found, the symptoms being due in one 
case to thrombosis of the left iliac vein, while in the others their 
cause was not found. In many of these cases the leucocytosis was 
very transitory, and without frequent (almost hourly) counts would 
have been overlooked. 

In the series of cases of typhoid perforation reported by Shat- 
tuck. Warren, and Cobb (Boston Medical and Surgical Journal, 
June 28th, 1900) there are four cases of general peritonitis with no 



204 



SPECIAL PATHOLOGY OF THE BLOOD. 



leucocytosis (3,800, 5,400, 7,300, and 8,000), and four eases with 
leucocytosis (14,000, 16,000, 17,200, and 23,000). Two cases with 
leucocytosis (14,300 and 13,200) showed at operation a perforation 
protected by local adliesions. In most of these only one count is 
recorded, so that the observations are of little value. 

There is no doubt that leucocytosis does occasionally occur when 
no complication exists so far as lue can ascertain during life. Four 
of the cases over 11,000 (see the above table) were counted re- 
peatedly and complications were carefully sought for, but none 
were found. The most striking case showed the following counts : 



October 3d 13,100 

4th 13,000 

5tli 16,500 

7th 13,800 

8th 11,200 

10th 10,600 

13th 13,500 

15tli 17,700 

" 17th 15,500, death; autopsy. 



The autopsy showed typical typhoid lesions and nothing else.' 
Another and much milder case showed 11,000-12,000 white cells 
constantly for over two weeks, and no cause could be found to ac- 
count for it. 

The great rarity of such cases and constant association of leuco- 
cytosis with any of the numerous complications which we can recog- 
nize, rather inclines me to the belief that in all the cases in which 
leucocytosis exists constantly, some complication really is present 
though unrecognized. The possibility of a secondary septic infec- 
tion, of an osteomyelitis, or phlebitis of internal veins is very 
difficult to exclude. 

3. Furuncidosis. — Thayer records 7 cases in all, of which the 
leucocyte count is very slightly raised tvhen ive comjjare it icith 
that usually found in tijphoid {e.g., 9,000,10,000, 10,200, 10,600, 
etc.). 

4. Tltromhosis — 6 cases in Thayer's study are of especial inter- 
est, because the leucocytosis with which each was associated ap- 
peared ill 3 cases earlier than any of the localizing symptoms, such 
as pain and oedema. 

The counts varied from 8,000 and 21,000 iii femoral phlebitis 

^ Thrombosis of internal veins and osteomyelitis were not carefully searclied 
for at autopsy and may have existed. 



TYPHOID FEVER. 



205 



to 24,800 in plugging of the iliac vein. I have had two similar 
cases. 

5. Pleurisy — 5 cases, all showed slight leucocytosis (10,000- 
12,000). Only in the purulent cases (empyema) was the count 
higher (23,000, 18,000). In one case the tapping revealed a bloody 
and purulent fluid containing only typhoid bacilli. After the tap- 
pmg the leucocytes rose to 44,500. 

In most of these cases the percentages of the different varieties 
of leucocytes was but little affected (e.g., 68 per cent of polynuclear 
cells and 1.8 per cent of eosinophiles with a count of 23,000 leuco- 
cytes. This is not an ordinary leucocytosis. 

6. Fneumonia — 5 cases, 3 with leucocytosis, 2 without it (ter- 
minal infections). Both of those without leucocytosis and 2 of 
the others proved fatal. The counts were 35,000, 38,000, 8,200, 
4,000, and 6,000. The neutrophiles were not increased as much as 
in ordinary leucocytosis. Ttirck records a case with but 1,600 leu- 
cocytes despite lobar pneumonia, and Kohler mentions several simi- 
lar cases. 

7. Bronchitis (severe) and Broncho-pneumonia — 4 cases, 3 
showed leucocytosis (16,600, 17,200, 18,200). 

8. Periostitis — 3 cases with leucocytosis reaching 22,000, 17,600, 
and 13,000 (only 72 per cent of polynuclear cells in first case). 

9. Suhmaxillary Abscess (streptococcus) with a maximum count 
of 18,200 which developed late in the course of the process. In 
another case with perforation peritonitis, the submaxillary abscess 
(staphylococcus and typhoid bacillus) did not produce any rise in 
the leucocytes. 

10. Otitis Media — 2 cases with leucocytosis of 15,600 and 11,- 
800 (maximal). I have had 10 cases with maximal counts of 
16,400, 14,000, 11,200. 

11. Parotitis — 3 cases, no leucocytosis in 2; in the other 30,- 
500 (general infection with the staphylococcus aureus found at 
autopsy. 

12. Perirectal Abscess — 25,100 leucocytes. In one of my cases 
(moribund) a large ischio-rectal abscess developed without produc- 
ing any leucocytosis. 

13. Pericarditis (dry) — 11,500 leucocytes. 

14. Bed- Sores (3) — 16,000 leucocytes (average). 

15. Conjunctivitis — 9,330 lucocytes (polynuclear cells 74 per 
cent. 



206 



SPECIAL PATHOLOGY OF THE BLOOD. 



16. Cliolccijtititis cases, all showing leucocytosis ; 28,;'500, 
21,200, and 14,400 (maximal). 

17. Cystitis ~o cases, 1 with marked leucocytosis; 18,000. 

18. Urethritis — o cases, 1 with 13,700 leucocytes, of which 5.5 
per cent were eosinophiles. 

19. Titherculosis (pulmonary) — 1 case w4th 14, 200 leucocytes, of 
which only 55 per cent were polynuclear. Tlirck records a similar 
case with a normal leucocyte count. Pregnancy and peripheral 
neuritis seemed to have no especial effect on the blood. 

Qualitative Changes. 
Red Corpuscles. — Tlirck notes "the relatively frequent presence 
of marked differences in the size of the red cells with very numer- 
ous dwarf forms; occasionally poikilocytosis and polychromato- 
philia," i.e., the changes common to all varieties of secondary anae- 
mia. 

White Cells. — Thayer's extensive and painstaking studies are 
exhibited in the following table : 

Table XIT. 





Counts. 


Polymorpho- 
nuclear 
neutrophiles, 
per cent. 


Small 
mono- 
nuclear, 
per cent. 


Large 
mono- 
nuclear, 
per cent. 


Eosinophiles, 
per cent. 


First week of fever. . . . 


12 


74 


13 


12 


0.5 


Second " " .... 


39 


71 


14 


13 


0.8 


Third " " .... 


34 


66 


21 


11 


0.3 


Fourth " " 


19 


65 


20 


14 


0.4 


Fifth " " .... 


8 


62 


18 


19 


0.3 


Sixth " " .... 


4 


58 


22 


13 


6.0! 


First week apyrexia . . . 


12 


61 


21 


15 


3.0 


Second " " 


IV 


49 


31 


17 


2.3 


Third " 


6 


57 


15 


23 


3.5 



These averages, however, cover up some aberrant percentages. 
For example, there was one case which in the first week showed 
15,000 leucocytes, of which 92.3 per cent were polymorphonuclear 
neutrophiles. No complication could be found. The lymphocytes 
"vvere but 7.7 per cent, and the eosinophiles had altogether disap- 
peared. Nine days after defervescence the leucocytes were 9,000, 
with 48.3 per cent of neutrophiles, 43.1 per cent lymphocytes, while 
the eosinophiles had risen to 8.6 per cent. 

High percentages of polymorphonuclear neutropiles sometimes 
occurred without an increase in the total count, e.g., in the second 



TYPHOID FEVER. 



207 



week a case with 8,000 leucocytes, of which 94.4 per cent were 
potymorphoniiclear, and in the third week a case with 4,000 leuco- 
cytes, of which 82 per cent were polymorphonuclear. 

In the ninth week one case showed 12.7 per cent of eosinophiles 
with 70.4 per cent of polymorphonuclear neutrophiles. 

Summmg up Thayer' s observations, we find : 

1. A steady diminution in the polymorphonuclears, the lowest 
point being reached at the end of the pyrexia. This is an absolute 
diminution. 

2. A relative increase in the lymphocytes, especially the larger 
forms ; absolutely their number is not much changed. 

3. A reduction (relative and absolute) of the eosinophilic cells 
during the pyrexia followed by an increase in convalescence, which 
may amount to a considerable eosinophilia. 

Ttirck's results are practically the same. He adds that eosino- 
philes may actually disappear from the blood at the height of the 
disease, and considers that their reappearance or increase previous 
to defervescence augurs a relatively short course for the fever, and 
(aside from the occurrence of complications) a good prognosis. 
Myelocytes and Reizungsformen were occasionally present in his 
preparations, even in a case with a leucopenia of 4,200 and but 52 
per cent of polymorphonuclear neutrophiles. 

Summarif. 

1. The red cells suffer to the extent of about 1,000,000 in the 
course of an average case, the reduction taking place gradually, and 
being most marked at the end of defervescence in most cases. 
Sweating, vomiting, or diarrhoea may cause considerable transient 
elevation in the count of red cells, while sudden losses follow intes- 
tinal haemorrhage. Occasionally a very severe post-febrile ansemia. 
occurs, the red cells being reduced nearly to 1,000,000 with the 
qualitative changes of a grave secondary anaemia. In most cases 
the qualitative changes are slight. 

2. Haemoglobin, as in most anaemias, suffers somewhat more than 
the number of red cells. 

3. The number of leucocytes is subnormal throughout the dis- 
ease, averaging about 5,000 at its height, though much lower figures 
are common. This leucopenia progresses with the severity and 
duration of the infection. Cold baths cause an immediate transient 
increase in the number of leucocytes in the peripheral circulation, 



208 



SPECIAL PATHOLOGY OF THE BLOOD. 



an increase which may amount to double or triple the number before 
the bath. 

Differential counts show, during the febrile period, a progressive 
diminution in the number and percentage of the polynuclear cells, 
with a corresponding rise in the percentage of lymphocytes and 
large mononuclear cells, and a great diminution or even disappear- 
ance of the eosinophiles. In convalescence the percentage of eosino- 
philes markedly increases, often before the other forms have re- 
sumed their normal numbers. 

4. Most complications, especially inflammations, produce a leu- 
cocytosis, but a particularly malignant infection may be followed by 
no increase and even by a diminution in the number of leucocytes. 
In many of the leucocytoses following complications the percentage 
of polymorphonuclear cells does not rise. 

Diagriostic Value. 

There are few diseases (outside of those knoAvn as diseases of 
the blood itself) in which the blood count is so often of value in 
diagnosis. The diagnosis of typhoid fever is made by exclusion — 
exclusion of other causes of fever and of local inflammatory processes 
in particular. 

1. In this process of exclusion, the blood is a most powerful 
adjuvant, inasmuch as almost all local inflammatory processes have 
leucocytosis, ivhile typhoid (uncomplicated) does not. I recall two 
cases in which the chart and symptoms pointed to typhoid, but in 
which the persistent marked leucocytosis directed attention to the 
search for an inflammatory focus. Both were at first unattended 
with pain, tenderness, or other localizing symptom, but later signs 
and symptoms began to point to the liver, from which pus was 
evacuated by puncture. These cases of abscess of the liver are typi- 
cal of the value of blood examination for any deep-seated suppu- 
ration. I have seen good clinicians puzzled for twenty-four hours 
over the diagnosis between appendicitis and typhoid, but the indi- 
cation of the blood count was always fulfilled. Fysemic or septi- 
ceemic processes are usually distinguishable from typhoid by the 
same test — the presence of leucocytosis in the former. 

Of the value of the blood in distinguishing certain cases of pneu- 
monia from typhoid I have already spoken on p. 195. 

2. Aside from local or general pyogenic infections perhaps the 
disease most often confounded with typhoid is malaria. This is 



TYPHOID FEVER. 



209 



especially the case in the southern part of this countryj where for 
want of proper blood examination the confusion of the two diseases 
is indicated in such a term as " typho-malarial fever." Malaria 
and typhoid are alike in having no leucocytosis, but the presence 
of the malarial parasite is an absolute test and in marked cases is 
always decisive. Very mild cases of malaria may show so few 
organisms in the peripheral circulation that without prolonged 
search they cannot be found, and in the severest types of all, the 
organisms are not very abundant. In the vast majority of cases, 
however, the organism can be readily found and our diagnosis made 
certain. 

3. Tuberculosis, local or miliary, if uncomplicated by any pyo- 
genic organisms, cannot be distinguished from typhoid by the blood 
count alone, as neither disease shows leucocytosis, but here the 
Widal reaction (see p. 458), comes to our rescue. 

A large proportion of lymphocytes is commoner in typhoid than 
in tuberculosis, but it may occur in either disease. In the majority 
of cases, however, tuberculosis is complicated with septicaemia from 
a secondary pyogenic infection, and is then easily distinguished by 
the existence of leucocytosis. 

4. Typhus fever has not been well studied and the reports of 
its blood condition are contradictory. At present we cannot say 
whether or not it can be distinguished from typhoid by the blood 
examination. In most cases the absence of a serum reaction will 
exclude typhus. 

5. Two cases of erythema nodosum with fever between 101° and 
103° gave me trouble in diagnosis lately. In both the blood was 
normal and differed from typhoid only by the absence of a serum 
reaction. Thayer has reported a similar case {loc. cit., p. 530), in 
which, however, there was a marked leucocytosis throughout. 

6. TricMniasis may run a course quite indistinguishable clini- 
cally from that of typhoid, but the presence in trichiniasis of a leu- 
cocytosis with marked eosinophilia and the absence of Widal' s reac- 
tion Avill decide any case of doubt. 

7. Most auto-intoxications (ptomain poisoning) produce leuco- 
cytosis, and can therefore be distinguished from typhoid. 

8. Meningitis, especially in its epidemic cerebro-spinal f orm, has 
many symptoms like those of typhoid, but it always produces leuco- 
cytosis, and is never associated with Widal' s serum reaction. 

9. From influenza typhoid cannot be distinguished by the blood 

14 



210 



SPECIAL PATHOLOGY OF THE BLOOD. 



count, as neither of them produces leucocytosis. Here the blood 
gives aid only through the serum reaction, 

10. Acute Infectious Di/senterij may present (especially in the 
tropics) many features that remind us of typhoid. As a rule it 
produces no leucocytosis, but it is distinguishable from typhoid by 
the presence of Widal's reaction in the latter. 

The occurrence of complications in typhoid may mask its char- 
acteristic blood changes so as to make the blood useless in diagnosis; 
but in most early cases, in which the diagnosis is especially important 
and difficult, the blood shows no leucocytosis and is therefore of 
great value in the exclusion of other diseases. 

Fro gnosis. 

In prognosis Naegeli {Deut. Arch, fur Mm. Med., vol. lxvii.,p. 
279) agrees with Tiirck in regarding the persistence or early reap- 
pearance of eosinophiles as a favorable sign, and believes that a 
normal number of polynuclear cells is a good sign when the outlook 
is more serious, if the leucocyte count is very low and does not in- 
crease during complications. 

DIPHTHERIA. 

Bacilli of diphtheria in the circulating blood are practically 
never to be found. 

The specific gravity, according to Grawitz, is above normal at 
the height of the disease. He obtained the same result experi- 
mentally by injecting cultures of the Klebs-Loffler bacillus into 
dogs and rabbits. He concludes that the poison of the disease is 
lymjohagogic and so concentrates the blood. 

Bed Coiyuscles. — Morse's' investigations show an average of 
5,100,000 in twenty cases counted during the first week of the dis- 
ease and of 5,150,000 in 10 cases during the second and third week 
of the disease— practically normal figures. 

These are the first systematic'' investigations of the red cells in 
diphtheria and are confirmed by the reports of Ewing, Engel, and 
Billings. The latter observer in counts made in seven cases during 
the tirst fii^e days of illness found an average of 5,600,000-f- I'ed 
cells per cubic millimetre. During the first five to ten days after 

' Boston Medical and Surgical Journal, March 7th, 1895. 
2 Earlier reports are faulty as to technique. 



DIPHTHERIA. 



211 



this, the same cases showed an average loss of 510,000 cells per 
cubic millimetre ; live out of the seven showing coni^iderable losses, 
two remaining about the same. These were cases treated without 
antitoxin. The two cases showing no loss of red cells were botli 
very mild, one having no membrane at any time. The diminution 
ranged from 470,000 (third day) to 2,040,000 (sixth day). As a 
rule no diminution can be made out until after the third or fourth 
day. 

Out of twenty-three cases treated with antitoxin and each 
counted several times over, only three showed any considerable 
diminution in the red cells and these lost less than 400,000 each, 
not much beyond the limit of error (200,000) allowed for by the 
investigator, and all of them severe cases. Six patients who were 
ansemic when admitted (average = 4, 640,000) showed a steady rise 
in the red cells as the disease (treated with antitoxin) progressed. 

It is evident from these figures that antitoxin largely prevents 
the anaemia which usually develops in the first five to ten days. In 
cases not treated with antitoxin the regeneration from the resultmg 
anaemia is slow. Healthy individuals injected with antitoxin 
showed a very moderate reduction in the red cells in about one-half 
the cases, the greatest loss being 932,000 per cubic millimetre (fif- 
teen cases counted by Billings). 

Qualitative Changes. — Billings' careful study of stained speci- 
mens showed no deformities in size or shape and no nucleated red 
cells, but Engel has found normoblasts. Polychromatophilic red 
corpuscles Avere very few in the cases in which antitoxin was 
used, but more numerous when it was not used. 

Ha'}))0(jJohiu . — Here again the most thorough investigations are 
those of Billings. In cases treated without antitoxin there w^as an 
average loss of ten per cent, regained in part during convalescence, 
but as usual reaching normal later than the count of corpuscles. 
When antitoxin was given, the diminution of haemoglobin was less 
marked, but when the decrease did occur the return to normal was 
slow compared to that of the red cells, even when the patients were 
up and about and apparently well. 

ITliite Corpuseles. — Leaving out the older observations in which 
the technique was probably faulty, the principal investigators are 
Morse, Ewing, Gabritschewsky, Billings, File, and Engel. 

. All agree that a considerable leucocjrtosis is present in most cases 
— 34 out of 36 of Billings' cases, 26 out of 30 of Morse's (the latter 



212 



SPECIAL PATHOLOGY OF THE BLOOD. 



made but one count in each case), 49 out of 53 of Ewing's. In a 
general way, the severest cases show the greatest leucocytosis, but 
it does not follow the pulse, temperature, nor the extent of the 
membrane, and "the ordinary clinical examination of the patient 
is of much greater value in . . . prognosis . . . than any infor- 
mation to be gained from the examination of the blood. The latter 
is simply confirmatory, never indispensable" (Billings). Morse's 
conclusions are the same, although he considers that with notable 
exceptions the amount of membrane is a rough measure of the de- 
gree of leucocytosis. He finds no correspondence between the glan- 
dular swellings and the degree of leucocytosis, though he noted 
that "in the fatal 'septic ' cases with greatly enlarged glands," very 
high counts were present. Other cases with little or no enlarge- 
ment of glands showed equally high counts, however. 

Ewing's 4 cases without leucocytosis were all mild, but of Bil- 
lings' 2 cases without leucocytosis one was the severest of his whole 
series, while the other was mild. Of Morse's 4 cases without leu- 
cocytosis 3 were mild and 1 was severe. Gabritschewsky's 14 cases 
all showed leucocytosis. 

Putting the results of these four observers together we see that 
when leucocytosis is absent the cases are either very mild or very 
severe, conditions analogous to those to be noted in pneumonia and 
septicsemia. The counts m recent epidemics range from normal to 
48,000 (Morse) or to 38,600 (Billings). Felsenthal ' found 148,229 
per cubic millimetre in one case, and Bouchut's^ counts are often 
over 75,000. 

In a general way the counts rise while the disease progresses 
and fall gradually as improvement goes on, disappearing after the 
membrane. "The leucocytosis is well marked by the third day 
and very likely earlier" (Morse). Billings found an increase after 
one day's illness, but usually less than was present later in the dis- 
ease ; one of his cases, however, had a higher count on the first day 
of the disease than on any subsequent day, though no antitoxin was 
given. 

The injection of antitoxin has apparently no effect upon the 
leucocyte count (strange to say) except in the first twenty-four 
hours after its use. Immediately, i.e., within thirty minutes after 
an injection, the leucocytes are stated by Ewing to be considerably 

1 Archiv f. Kinderheiik., vol. xv., p. 78, 1893. 
^comptes Rendus, 1877, Ixxv., No. 3. 



DIPHTHERIA. 



213 



diininisliecl, but the leucocyte curve does not reach normal any 
sooner than m cases in which no antitoxin is given, although it be- 
gins to fall in the majority of cases after the injection. The same 
thing (according to Billings) takes place without antitoxin. 

The leucocytes of healthy persons are likewise unaffected by 
antitoxin injections. 

Qualitative Changes.— All authors agree that in most cases the 
neutrophiles are increased. Morse found an average of 80 per cent 
in 26 of his 30 cases. Of the other 4, 1 was normal and 3 were sub- 
normal (58, 59, and 59 per cent) ; 2 of these were convalescent, the 
other had been sick a week and had 12,000 white cells per cubic 
millimetre. A marked lymphocytosis was present in 2 of Ewing's 
53 cases, 43,200, and 13,950 absolute.^ In Billings' cases the poly- 
morphonuclear varieties averaged 80 per cent and the lymphocytes 
19 per cent, the eosinophiles being reduced to 1 per cent on the 
average and often being entirely absent. With Morse eosinophiles 
averaged 2 per cent. 

The proportion of polymorphonuclear cells is usually directly 
proportional to the total increase of leucocytes. 

Ewing thinks that " the staining reaction of the leucocytes is an 
accurate measure of the severity of the diphtheritic infection," and 
this staining reaction he finds increased in favorable cases by the 
injection of antitoxin. 

Billings did not find any such changes in "staining reaction," 
though he claims to have carefully followed out Ewing's procedures. 

Engel ^ found that antitoxin at first slightly increased the per- 
centage of lymphocytes, and sometimes this increase was very 
marked. In one case the lymphocytes increased from 24 to 65 per 
cent after antitoxin. 

The point on which he specially insists is the presence of con- 
siderable numbers of myelocytes in fatal cases. 

Of the patients examined by him 17 died, and 9 of these had 
from 3.6 to 16.8 myelocytes in everyone hundred leucocytes. My- 
elocytes were also present in some of the patients who recovered, 
but in smaller numbers (1.3 to 1.5 per cent). 

In one case he found on the third day of the disease 4. 3 per cent 
of myelocytes, and from this point the percentage gradually rose to 

* In a case of Rieder's, aged three years, the lymphocytes rose from 19 per 
cent during the fever to 64 per cent in convalescence. 
^Gesc'Uoch. f. innere Med., Berlin, July 6th, 1896. 



214 



SPECIAL PATHOLOGY OF THE BLOOD. 



13.8 per cent, and then fell, there being 1.7 per cent present at the 
time of death. An abscess occurring in the case showed only the 
usual polymorphonuclear leucocytes in its contents. He concluded 
that a large percentage of myelocytes is a bad prognostic sign in 
au}^ case. 

Myelocytes are not mentioned m any of the numerous differential 
counts made hj Gabritschewsky, Ewing, Morse, and Billings, so that 
Engel's observation is so far unique. 

Sumrna?'//. 

1. Moderate anaemia, especially in cases treated without anti- 
toxin. Regeneration is slow. . 

2. Leucocytosis, very roughly parallel to the severity of the dis- 
ease, unaffected by antitoxin treatanent, gradually decreasing as the 
disease passes off, sometimes absent in very mild or very severe 
cases. 

3. Polymorphonuclear leucocytes much increased during febrile 
stages, often diminished in convalescence. 

4. Myelocytes numerous in some severe cases. 

The blood examination has no diagnostic value so far as I can 
see ; in prognosis the absence of leucocytosis (except in obviously 
mild cases) and the presence of many myelocytes are apparently 
bad signs. 



CHAPTER IV. 



ACUTE INFECTIOUS DISEASES (CONTINUED). 

SCARLET FEVER. 

Heubner' noted hgemoglobinsemia in one case. Fibrin is not 
increased even at the height of the fever, provided inflammatory 
complications are absent. 

Red Cells. — Very little is to be found in literature upon the sub- 
ject. Kotschetkoff ^ noted a gradual diminution of the red cells to 
about 3,000,000, regeneration taking place in the course of not less 
than six weeks. Other observers have found little or no anaemia. 

Hayem^ estimates the average loss of red cells at 1,000,000. In 
mild cases he finds the lowest figures on the first day of normal 
temperature. In severer cases in which the fever comes down 
slowly, the red cells may not reach their minimum till twenty-four 
hours after the normal temperature is regained. 

Felsenthal^ in six cases found the count to be 4,500,000 to 
5,500,000— no considerable variation from normal. 

Zappert " in six cases found it to be from 3,920,000 to 4,500,000, 
an average of 4,150,000. Normoblasts are occasionally seen — as in 
one of Tiirck's cases, and the normal variations in size and shape 
are exaggerated. 

IVIiite Cells. — Most observers are agreed that leucocytosis is the 
rule, contrasting in this respect with measles, in which no leuco- 
cytosis occurs. The increase may be present even six days before 
the rash appears and attains its maximum two or three days after 
the eruption. In light cases it may sink to normal even before the 
fever is gone, while in severer cases it may persist several days after 
normal temperature is reached. Von Limbeck had a case in which 

^ Deut. Arch. f. khn. Med., vol. xxiii. 
2Ref. iu Petersburg, med. Woch., 1892, 1. 
^Loc. cit., p. 914. 

4 Arch. f. Kinderheilk., 1892, p. 80. 
^Zeit. f. khn. Med., 1893, p. 292. 



216 



SPECIAL PATHOLOGY OF THE BLOOD. 



the leucocytosis persisted for twelve days after the temperature had 
become normal, 'l^orty thousand per cubic millimetre is not un- 
usual in well-marked cases. Eieder's ten cases averaged 17,500; 
Felsenthal's six counts were between 18,000 and 30,000. My own 
are similar. 

In a general way the severest cases are apt to have the highest 
leucoc3rte counts ; the figures have no direct relation to the amount 
of fever, glandular swelling, or to complications in the ear or 
kidney. 

Qualitative Chanc/es. — The polymorphonuclear forms are in- 
creased, often to 90 per cent, soon falling except in the worst 
cases. The peculiar characteristic of the disease is the persistence 
of eosinophiles in all but the severest cases despite the increase of 
polymorphonuclear forms. The only other infections of which this 
is true are tetanus and acute articular rheumatism. They may run 
as high as 5 per cent during the fever, and are still more numerous 
in convalescence, remaining increased for six weeks. According to 
Kotschetkoff, disappearance of eosinophiles is a bad prognostic sign 
except at the very beginning of the fever, when they may be tem- 
porarily absent in favorable cases. Presumably they have some 
connection with the exanthem, eosinophilia being so common in 
connection with skin lesions. They may number 15 to 20 per cent 
of the leucocytes in convalescence (Bensaude). Tlirck reports 14.3 
per cent (1,800 absolute) in one case and 13.3 (800 absolute) in an- 
other. Felsenthal's average is 5 per cent; Zappert's, 3 percent. 
The lymphocytes are decreased proportionately to the severity of 
the case, the worst cases showing only 2 to 4 per cent. 

An increase of eosinophiles during a scarlatinal nephritis is re- 
garded by Neusser and his pupils as a favorable sign, and their ab- 
sence as ominous. In ordinary eases without nephritis they reach 
their maximum in the second or third week and are not normal till 
the sixth. In the active stages of the disease myelocytes, transi- 
tional neutrophiles, and " stimulation forms " occur. 

Sifnnnar}/. 

Moderate ansemia. 

Leucocytosis beginning before the erujDtion and often lasting into 
convalescence. 

Eosinophiles said to be increased in favorable cases, absent in 
bad cases. 



MEASLES. 



217 



Diaffnostic and Prognostic Value. 

1. The chief importance of the blood examination is in distin- 
guishing the disease from measles and the eruptions of other dis- 
eases. Measles has no leucocytosis. 

2. Whether the prognostic significance attached by Neusser and 
others to the percentage of eosinophiles is genuine or not, cannot as 
yet be positively stated. 

MEASLES. 

In mild cases the blood shows no changes at all. When bron- 
chitis, coryza, and conjunctivitis are very marked, fibrin may be 
increased. 

Bed Cells. — In mild cases no change — never over 400,000 or 
500, 000 red cells are lost (Hayem) . FelsenthaP s eight cases showed 
counts of 5,000,000 to 5,500,000. 

White Cells. — There is no leucocytosis, often a leucopenia dur- 
ing the eruptive stage. In convalescence the lymphocytes and es- 
pecially the large mononuclear forms are increased. Felsenthal in 
eight cases found the count normal or diminished. Pee found but 
4,000 in a case with a fever of 102.7°. Rieder's eight cases aver- 
aged 7,500, being lowest at the height of the disease and increasing 
as fever passed off. Complication with catarrhal pneumonia or a 
very bad bronchitis and coryza, may slightly raise the count. The 
eosinophiles, contrary to the example of scarlet fever, are often 
diminished during fever. 

The Massachusetts General Hospital records furnish the follow- 
ing counts : 

Table XIII. — Measles. 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
hfemo- 
globin. 


Remarks. 


4 






11,000 




Rash out; temp. 104°. 


11 






10,100 




38 


M. 


4,700,000 


9,000 


65 


" Black measles " ; petechiae. 


8 


M. 




9,000 




Differential count normal. 


21 






8,200 




Rash out; temp. 103°. 


23 


F*. 




8,000 


68 


104° ; eruption out. 


4 


M. 


5,000,000 


7,000 


60 


Eruption just out. 


10 


M. 




6,000 




103°; three days before the erup- 












tion ; differential count normal. 








6,000 




Eruption out one day. 








6,000 




Eruption out three days. 


53 


F. 




3,500 




33 


F. 




3,500 


67 




14 






1,400 







218 



SPECIAL PATHOLOGY OF THE BLOOD. 



Felsenthal found tlie polymori^hoiiuclear cells much increased 
and eosinophiles never over one per cent. In my own cases the 
differential counts were normal. The vdluf of the blood examina- 
tion is considerable in excluding scarlet fever, diphtheria, and 
syphilitic roseola, all of which show leucocytosis. It cannot ap- 
parently be distinguished by the blood count from rbihdn (German 
measles), in two cases of which, seen at the Massachusetts General 
Hospital, the white cells were G.OOO and 8,000 respectively. 

mu:mps. 

Five cases of mumps under my care showed no leucocytosis. 
Tiirck on the other hand records one case with marked leucocytosis. 
Data are very scanty regarding the disease. 

WHOOPIXG-COUGH. 

Meunier {ArcJiiv. d. JIaladies V Enfance, April, 1898) re- 
ported studies in 102 cases of Avhoo^^ing-cough. Lymphocytosis is 
early a^nd constant. The counts averaged 22,700 in the cases ex- 
amined during the catarrhal stage and before the advent of typical 
"whooping" paroxysms. In the paroxysmal stage the leucocytes 
average 40.000 — the maximmn being 51,250. In infants under four 
years the leucocytosis is far more intense than in older children. 
After the fourth year the count runs from 12,000 to 18,000, All 
the varieties of leucocytes are increased, but the lymphocytes are 
relatively as well as absolutely increased— a true lymphocytosis 
perhaps due to stimulation of the bronchial lymph glands. 

Meunier found no such changes in the blood of cases bronchitis 
or tracheitis, and suggests that the blood count maybe of use in the 
investigation of doubtful epidemics in schools or hospitals. 

The following case exemplifies these rules (see also p. 195). 



Table XIY. — Whoopixg-Cough. 



Age. 


Red cells. 






3 

0 


5,192,000 


75.000 
26,500 

32,800 


47 


July 23(1. 
Polynuclear. 42. 
Lymphocytes, 57. 
Eosinophiles. 1. 
August 19th. 
August 31st. 
Polynuclear, 56. 
Lymphocytes, 43. 
Eosinophiles, 1. 
Lymphocytes. 69. 







SMALLPOX. 



219 



These results have been confirmed by De Amicis, Cima, and 
others. 

SMALLPOX (VARIOLA). 

Red Cells. — According to Hayem no other fever is so destructive 
of red cells. During the fever the count is normal or increased, but 
when the temperature falls permanently the number of red cells falls 
suddenly, whether because the blood is diluted (see above, p. 188) 
or by a real destruction. From this time on the cells are slowly 
regenerated; even at the fifteenth day Hayem found them consider- 
ably below normal. 

In hemorrhagic cases the anaemia comes on more quickly, its 
degree depending on the amount of hemorrhage. In one patient, 
dying on the seventh day of the eruption, Hayem found but 2,000,- 
000 red cells, in another at the same stage, 4,600,000. 

Fibrin is not increased until the stage of suppuration is reached. 

Leucocytes. 

In Pick's report on 42 cases no leucocytosis is recorded until the 
appearance of vesicles. 

Elaborate studies in the blood of smallpox have lately been pub- 
lished by Weil,' and by Courmont and Montagard.^ These studies 
are concerned especially with the leucocytes. In Weil's series of 
36 cases the counts ranged between 6,000 and 10,000 in 6 cases, 
between 6,000 and 13,000 in 13 cases, exceeding 15,000 in 9 cases, 
exceeding 20,000 in 3 cases, 25,000 in 3 cases, 30,000 in 1 case, 
35,000 in 1 case. 

One case ranged from 3,000 to 6,000 during the whole course of 
the disease, except on the day of vesiculation (24,000), but this is 
very rare, and the leucocytes are usually increased from the begin- 
ning. The increase is usually most intense at the time of vesicula- 
tion and from that time does not vary notably until after pustulation, 
when it slowly declines until in convalescence a subnormal count is 
reached. In hemorrhagic cases the increase is usually less marked. 

A sudden drop in the leucocyte count may occur in the fatal 
suppurating or hemorrhagic forms. For example, in 2 fatal sup- 
purating cases the leucocytes dropped from 24,000 and 18,000 to 
6,200. In one hemorrhagic case on the dying day counts of 6,200, 

1 Soc. de Biol., .lune 29th, 1900. 

2Soc. de Biol., June 22d, 1900; July 6th, 1900. 



220 



SPECIAL PATHOLOGY OF THE BLOOD 



GjOOO, and 4,400 Avere recorded. A .siiddeu drojj in the leueoeytcs 
is then a bad prognostic sign (from this opinion Courmont and 
Montagard dissent i . 

Complications occurring in convalescence produce a second rise 
in the leucocytes. 

Qurditnfice CJionrjes. 

The most significant fact in the blood of variola, according to the 
Tvriters already quoted, is the increase in mononuclear cells. The 
percentage of polynuclear cells, instead of being increased as inmost 
infectious diseases, is from the outset diminished {i.e., 40 to 50 per 
cent), and may go as Ioav as 14 to 20 i^er cent. Eosinophiles range 
from normal (1-3 per cent) at the beginning of the disease, down- 
ward. They are lowest just before desquamation. In convales- 
cence they are often slightly increased. 

Among the ''mononuclear cells '" the increase of Avhich is held 
by AVeil to be characteristic of the disease are : 

(r/) Small lymphocytes, 30-40 per cent. 

(h) Large mononuclear, 4-10 per cent. 

(c) ^Myelocytes, 2-10 per cent (even 25 ^oer cent in hemorrhagic 
cases). 

(cJ) Tiirck's Eeizungsformen,'' 2-10 per cent. 

During suppuration and desiccation the mast cells are sometimes 
increased (5 per centj. The abnormal leucocytes — (c) and {d) above 
— are present from the very beginning of the disease and forma very 
characteristic part of the blood picture. They persist through p^i^- 
tulation and diminish only in convalescence. They are present in 
mild varioloids as well as in severe variola. Complications (pneu- 
mococcus or streptococcus septicaemia) do not materially modify the 
blood picture, unless they occur late in convalescence. In con- 
valescence a 23olynuclear leucocytosis may result from sup23urative 
complications. 

Diarjnostic Value. 
In excluding scarlatina, measles, purpura, syphilis, erythema 
multiforme, the blood is conclusive. Varicella, on the other hand, 
produces changes in the blood, which are precisely of the same type 
as those of variola, though less in degree. 

Vrjcciniri. 

The red cells and haemoglobin shew no constant variation after 
vaccination CSobotka). but the leucocvtes are alwavs increased, the 



ACUTE ARTICULAR RHEUMATISM. 



221 



leucocYtosis appearing in two waves, — one (varying from 12,000 to 
23,000) which occurs from the third to the seventh day, and a 
second on the tenth to twelfth days (10,000 to 17,500). 

VARICELLA (CHICKEX-POX). 

The only observation of which I am aware is that reported by 
EngeL' In a child of live he found during the height of the pus- 
tular stage a moderate leucocytosis, with 67 j)er cent of neutrophiles 
(high for a young child), and no eosinophiles. Three days later, as 
the pustules were healing the neutrophiles had sunk to 47 per cent 
(normal for that age) and the eosinophiles had risen to 16 per cent. 

ACUTE ARTICULAR RHEU^IATISM. 

According to Hayem and Garrod - the blood constitutes, as in 
syphilis, a most valuable measure of the intensity of the sickness, 
wMgOi is parallel to the severity of the blood-changes rather than 
to the number of joints affected. The fever, the intensity of the 
lesions, and the state of the blood run parallel, in a general way, 
but the degree of anaemia is a more delicate index of the patient's 
condition than even the temperature chart (Garrod). 

Tlie Blood OS a Whole. 

Fibrin is greatly increased. In no other disease except in pneu- 
monia is the network thicker or more rapid in formation. Accord- 
ing to Maclagan, this is to be explained by an increase of tissue 
metamorphosis. Coagulation, on the other hand, is not quicker, but 
slower than usual. 

Lactic acid is present in excess, but cannot be clinically esti- 
mated, nor is its excess peculiar to this disease. 

The alkalinity of the blood had been reported diminished, but 
the technique is not considered reliable by the best observers. 

Red Cells. — Hayem^ and Osier"' state that the poison of acute 
rheumatism is a powerful and rapid destroyer of red cells. In acute 
cases, according to Hayem, the red cells lose at least 1,000,000 of 
their number, and in cases which drag along and relapse the loss is 

1 latli Cong, fur innere Med., 189T. 

-British Medical .Journal. May 28th. 1892. 

^Loc. cit., p. 917. -^"Practice of Medicine," 1895. 



222 



SPECIAL PATHOLOGY OF THE BLOOD. 



from 1,500,000 to 2,000,000. When an attack is cut short by 
salicylate treatment the drain on the corpuscles is stopped. 
Tlirck's careful studies led him to the same conclusions. Eed cells 
and haemoglobin are always markedly diminished during the fever, 
the haemoglobin especially, and after the attack a post-febrile anae- 
mia of varying severity is always left. 

So far as my experience goes, this diminution does not seem to 
occur in all cases. Many of my cases had been sick some weeks 
before the time when the count was made, yet the counts are not 
very low. The average count of red cells in the whole group of 
cases is 4,300,000. The lowest counts were 2,528,000 with 45 per 
cent of haemoglobin, 3,248,000 with 45 per cent of haemoglobin, 
3,456,000 with 50 per cent of haemoglobin, 3,332,000 with 45 per 
cent of haemoglobin, 3,468,000 with 36 per cent of haemoglobin, 
3,440,000 with 26 per cent of haemoglobin, 3,608,000 with 40 per 
cent of haemoglobin. Only 13 cases below 4,000,000 are recorded 
out of 113. According to Hayem, 4,000,000 is the usual count in 
acute cases and 3,000,000 to 3,500,000 in those which drag on and 
relapse. 

Qualitative Chaiujes. — Maragliano's so-called degenerative 
changes in the red cells have been observed in this disease, but are 
not very marked. Tlirck found erythroblasts in about a quarter of 
his cases. Deformities in the red cells are usually slight. 

Hceiiio(jlobin.—X^ in all secondary anaemias the corpuscles get 
thin and pale before they die, and hence the coloring matter is 
diminished more than the count. The average haemoglobin percen- 
tage in this series is sixty-three, and the color index .73. Hayem 
noted that, in some cases during convalescence, as the red corpus- 
cles slowly increase the color index remams low or even goes lower 
still. 

Leucocytes. — All observers agree that leucocytosis is the rule and 
that its degree is roughly parallel to the acuteness and severity of 
the attack (the individual's vigor of reaction is always a factor) and 
the amount of fever. Turck insists that complications (pneumonia, 
pericarditis, pleurisy) are present whenever the count rises over 
20,000, and in this he is supported by Ewing. Xo such complica- 
tions were discovered in the 22 cases of Table XV., B, which ex- 
ceed 20,000, but this table shows that in 80. 5 per cent of 113 caser, 
the leucocytosis was under 20,000. The following tables illustrate 
the variations of the leucocytes in a fairly typical way : 



ACUTE ARTICULAR RHEUMATISM. 22^ 
Table XV., A. — Acute Articular Rheumatism. 



White 
cells. 


Per cent 
haemo- 
g^lobin. 


31,500 


65 


27,800 


45 


37,000 


94 


26,000 


50 


24,500 


76 


21,000 


56 


20,000 


45 


19,«00 


60 


19,600 


45 


18,300 


70 


17,700 




17,400 


55 


17,000 


45 


16,301) 


58 


16 0(X) 


68 


15,\s00 


57 


15,200 


65 


15,000 


56 


15,000 


50 


15,OLtO 


58 


15,IXK) 


30 


14,500 


75 


14,5(M) 


40 


14,386 


60 


14]o:H) 


75 


14,000 




14,000 


54 


14,0(X) 


70 


13,500 


64 


13,2(K) 


65 


] 3,000 


50 


12,800 


55 


12,750 


68 


12,650 


65 


12,500 


65 


12,000 




12,000 


65 


11,600 


65 


11,500 


70 


1 1 500 


60 


1 1^300 


50 


11,(100 


80 


10,400 


45 


10,200 


50 


9.400 


40 


9,100 


45 


9,000 


33 


8,0! 10 


50 


7,000 


4i) 


6,800 




5,500 


58 


4,700 


26 




60 
46 




45 



Age. 



21 
20 
.•)9 

20 
33 
Adult. 
19 

23 
23 
49 
46 
21 
37 
24 
32 
13 
12 

8 
20 
22 
19. 
41 

9 
47 
25 
18 



30 
47 
27 
17 
27 
28 
33 
42 
33 
28 
10 
20 
36 
28 
Adult. 
29 
30 



Duration. 



5 weeks. 
........ 

? 

2 weeks. 



4 weeks. 



2 days. 



1 day. 

2 weeks. 



4 days. 



1 day. 
3 days. 

2 months 



1 month. 



4 weeks. 

3 days. 
1 week. 

10 days. 

4 weeks. 



3 weeks. 
9 weeks. 



Degree of 
inflammation. 



Red and hot. . . . 

9 



Tender and hot. 
Red and hot — 



Red and hot .. , 
Red and hot . . , 



Red and hot . . 



Red and hot 

Tender and hot. . 
No redness or 
heat. 



Swollen and ten- 
der. 



Very slight 

Hot and red — 



Some joints hot. 



Red 
cells. 



4,160,000 
3,832,000 
5,476,000 
4,392,01)0 
4,852,{HX) 
4,216,000 

3,248,(;0:l 

4,184,000 
3,792,000 
5,192,000 
4,800,(H)0 
4,934,000 
3,944,0(X) 
5.224,000 
4,60n,(iO(i 
4, s; 52. ()()() 
4,880,(100 
4,4(K),000 
3,972,000 
4,872,000 
5,336,000 
4,760,000 
4,397,000, 
4,210,000 
4,750,(XX) 
4,850,000: 
4,156,000 



4,172,00(^ 
4,580,000 
4,720,000 
3,456,000 
5,440,000 
4,320,000 
4,128,000 
5,320,000 

4,160,00' 
4,288,0(X) 
3,580,000 
4,()00,(){M) 
4,200.0110 
4,888,000 
5,48(),0;i0 
3,882,000 
4,056,000 
4,728,000 
4,312,000 
3,468,000 
4,716,000 
3,608,000 
3,768,000 
4,104,000 
3,440,000 
4,412,000 
4,240,0(X) 
2,528,000 



Remarks. 



Knees and one ankle. 
Patient pale. 



Died. 

Third day. 
Temperature, 102° 
Paronychia also. 



Cheeks rosy. 



Temperature 102°. 



Severe case. 
Seventieth day. 



Hands alone Involved. 



Mitral regurgitation. 



Fourth relapse. 
Specific gravity, 1.040. 



Twenty-second day. 



Table XV., B. — Acute Articular Rheumatism. 



White cells. Cases, 

Between 6,000 and 8,000 4 

8,000 " 10,000 9 

10,000 " 12,000 12 

12,000 " 14,000 14 

14,000 " 16,000 21 

16,000 " 18,000.... 23 



224 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XV., B.— Acute Articular Rheumatism {Continued). 



White cells. Cases. 

Between 18,000 and 20,000 8 

20,000 " 22,000.. 5 

22,000 " 24,000 5 

24,000 " 26,000 6 

26,000 " 28,000 % 

30,000 " 32,000 3 

38,000 " 40,000 1 



113 

Table XY., C. — Subacute Articular Rheumatism. 



o 


Age. 






1 


62 


2 


23 


3 


33 


4 


36 


5 


32 


6 


22 


7 


23 


8 


31 


9 


25 


10 


68 


11 


23 


12 


13 


13 


50 


14 


45 


15 


30 


16 


15 


17 


32 


18 


28 


19 


25 


20 


33 


21 


17 


22 


53 


23 


28 


24 




25 


Adult. 


26 


Adult. 



M 



Red cells. 



5,040,000 
4,750.000 
4,430,000 



4.644,000 
3,820,000 



4,684,000 

4,016,000 
4,188,000 



White 
cells. 



700 
700 
500 
200 
200 
600 
500 
200 
000 
200 
000 
900 
900 
500 
200 
800 
600 
000 
000 
400 
600 
500 
500 
100 
900 
000 
800 
200 
750 



Per cent 
haemo- 
globin. 



62 



60 
85 



70 
55 
45 
72 
60 
55 
100 

65 



60 
50 



65 

75 
60 



Remarks. 



First day. 
Fourth day. 



Sixth day. 



May 24th. 

May 28th ; mitral regurgitation. 



Temperature 100° 



Temperature 100.5°. 



Table XV., D. — Chronic Rheumatism, Chiefly Articular. 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 




1 


78 


F. 


9 


7,200 


V 




2 


19 


F, 


5,248,000 


8,300 


45 




3 


3j2 


F. 


9 


6,400 


9 




4 


58 


M. 


4,744,000 


6.500 


60 




5 


30 


F. 


9 


6,100 


9 




6 


20 


M. 


5.576,000 


9,800 


62 










Average = 


7,400 







ACUTE ARTICULAR RHEUMATISM. 225 



Table XV., E.— Muscular RheumatisiM. 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


1 


46 


M. 


4,580,0U0 


7,500 


70 




3 


52 




4,370,000 


4,000 


55 




3 


54 


M. 


4,360,000 


7,500 


75 




4 


38 


M. 


V 


6,600 


V 




5 


54 


M. 


3,820,000 


14,00f) 


58 


During febrile attacks. 


6 


27 


F. 




6,000 


? 


Lumbago. 




35 


M. 




5,700 


? 










Average = 


7,328 + 







The average leucocytosis in the acute cases is 16,200; in those 
mild and more chronic, so-called " subacute " cases the leucocytes 
range lower, averaging 9,760 ; while in chronic rheumatism, whether 
articular or muscular (including lumbago) , there is no increase at all 
(average = 7, 450). In acute cases the leucocytosis subsides with 
the joints, rising again if relapse or complication occurs. The 
polynuclear cells are absolutely increased with an absolute diminu- 
tion of the lymphocytes. The eosinophiles rarely disappear as in 
most infections. After the very earliest days (when they may be 
scanty or rarely absent) they are increased despite the fever and 
exudation. In convalescence they run even higher, 13.8 per cent 
(or 970 absolute) in one of Tlirck's cases. During the fever Turck 
noted myelocytes and stimulation forms as in other infections. 

Blood plates are much increased during the fever. 

In 25 cases of arthritis deformans treated at the Massachusetts 
General Hospital the blood was normal except for a slight deficiency 
of haemoglobin in two cases. 

Summary. 

Anaemia with leucocytosis, the degree of which is a measure of 
the severity of the infection. Fibrin much increased. 

Diagnostic Value. 

The blood tells us little if anjrthing that could not be learned in 
other ways. It does not differ at all from that of a septic arthritis, 
or from that of acute gonori'hceal arthritis. 

The only cases that I remember in which a blood examination 
has been valuable are the following : 

Case I. — The patient had muscular pains, fever, and a history 
of a malarial attack some months earlier. The question to be de- 
cided by the blood examination was between malaria and "rheu- 
15 



226 



SPECIAL PATHOLOGY OF THE BLOOD. 



matism." The leucocytes were 23,600 per cubic millimetre, TvMch 
made it clear that the case was neither malaria nor "rheumatism," 
since the former never increases the leucocytes and the latter could 
give so high a count only in case genuine (tri'u-idar inflammation 
were present. The case turned out to be croupous pneumonia 
which the high leucocyte count strongly suggested. 

Case 11. — The patient presented symptoms and signs of acute 
polyarticular rheumatism with fever. The fever came down under 
salicylates, but soon rose again, and the man became wildly delirious. 
His delirium persisted after the salicylate was sto23ped. Several 
joints continued swollen and tender. The fever was very moderate, 
ranging between 99° and 101°. There were no rose spots and no 
enlarged spleen. The question arose as to whether it was a case of 
sepsis with localization in the joints, or whether it was a case of ty- 
phoid supervening on an arthritis of some kind. The blood count, 
which was repeated several times, always showed a perfectly normal 
blood except for a slight aneemia. The subsequent course of the 
case, during which he remained for nearly three weeks more or less 
delirious, made it clear to Dr. F. C. Shattuck, under whose care the 
patient was, that the diagnosis was typhoid. 

Chronic rheumatism (muscular or articular) produces no constant 
blood changes appreciable by clinical methods (see Table XT. , D 
and E) . 

ASIATIC CHOLERA. 

In no other disease, so far as I am aware, has an acid reaction in 
the blood been reported. This is at the end of life. All observers 
agree that the alkalinity is at least greatly reduced. 

Our knowledge of the corpuscles is best summed up in Bier- 
nacki's^ study of thirty-eight cases. 

Red Cells. — In the stadium algidum, or stage of collapse, most 
of the symptoms are due to the great concentration of the blood 
from the loss of serous fluid in the stools. Hayem found the in- 
crease of red cells from this concentration to amount to from 1,000,- 
000 to 1,500,000 per cubic millimetre. 

Biernacki ' found 7,662,500 in one case twenty-four hours after 
the beginning of the disease. The S23ecific gravity may be as high 
as 1.071 or 1.072. 

White Cells. — Leucocytosis is present, not merely as the result 
of concentration, but as a genuine increase to at least double the 
normal count. Biernacki ^ found that cases with particularly high 
counts (40,000 to 60,000) were soon fatal, so that he considers a 
marked leucocytosis in the algid stage as a bad prognostic sign, al- 
'Deut. med. Woch., 1895, No. 48. 



ERYSIPELAS. 



227 



though patients also die with low leucocyte counts in this period. 
Such a leucocytosis does not occur in ordinary diarrhoea or dysen- 
tery. 

Leucocytosis is present as early as twelve hours from the first 
symptom and lasts at least as late as the sixth day. In the stage of 
reaction it usually decreases. In one very mild case reported by 
Biernacki there was not only no increase, but leucopenia (4,375 per 
cubic millimetre). 

The differential count shows from eighty-two to ninety-five per 
cent of adult cells and a corresponding diminution of the young 
forms. 

ERYSIPELAS. 

Ehrlich, Halla, Pee, Reinert, Eieder, and von Limbeck agree that 
leucocytosis is usually present in well-marked cases. Von Limbeck 
finds the " leucocyte curve " to run roughly parallel with the temper- 
ature chart, sometimes beginning to fall a little before the latter. 
The counts rarely run very high, yet Eeinert counted 39,627 in one 
case. Pee noted that the leucocyte count increases only while the 
process is spreading, and that the size of the count was a tolerably 
accurate measure of the severity of the case. 

Rieder found in seven cases an average of only 15,000 per cubic 
millimetre despite very high temperatures. In one case the leuco- 
cyte count remained high after the temperature had fallen, but in 
the others it anticipated the temperature. In one mild case he 
found no leucocytosis. Polymorphonuclear cells are greatly in- 
creased as in other forms of leucocytosis. Hayem noticed the same 
dependence of the leucocyte count upon the severity of the process. 



Table XYI. — Erysipelas. 



Case. 


Age, 


White cells. 


Remarks. 


1 


28 

25 
78 
29 
51 
17 
? 

21 


14,400 
14,450 
17,100 
17,300 
15,400 
16,600 
17,000 
14,000 
13,000 
12,700 
7,250 
6,200 


First day. 
Second day. 
Third day. 

Fourth day ; spreading. 
Temperature 105°. 


3 


3 


4 


5 


6 


7 


8 





228 



SPECIAL PATHOLOGY OF THE BLOOD. 



In eight cases at the Massachusetts General Hospital I found 
leucocytosis in all but two, and these two very mild cases. The 
polynuclears increase and the lymphocytes decrease as in most in- 
fections, and the usual abnormal forms (stimulation forms and 
myelocytes) maybe abundant. Ttirck records five per cent of mye- 
locytes (320 absolute). 

When the disease occurred in " scrofulous " cases, Hayem found 
only 7,000-8,000 leucocytes per cubic millimetre, while in cases 
with very extensive process and high fever 12,000-20,000 were 
present. He found also a loss of 500,000-1,000,000 in the count 
of the red cells, according to the severity of the case. This showed 
itself particularly just before the fall of the temperature. I have 
seen no reference by other writers to the condition of the red cells 
in this affection. 

TONSILLITIS (FOLLICULAR). 

Halla,^ Pick,^ and Pee^ found leucocytosis as a rule in uncom- 
plicated follicular tonsillitis ; Eieder found it in a case complicated 
with acute nephritis. 

The following table confirms these observations in the main, 
though in mild cases no leucocytosis was present. 



Table XVII. — Tonsillitis. 



d 


Age. 


p< 

CO 


Red cells. 


White 
cells. 


Per cent 
hasmo- 
globin. 


Remarks. 


1 


3 






34,400 














36,900 














36,300 






2 


7 






38,000 






3 


33 






33,100 




December 34th. Follicular. 










7,600 




December 36th. 


4 


18 






31,300 






5 


33 


F* 


4,368,000 


19,300 


35 




6 


33 




18,500 






7 


31 


F.' 




18,000 






8 


34 






18.000 




Acute foUicular. 


9 


37 


M. 




18,000 






10 


13 






17,300 




Streptococcus. 


11 


31 


F* 




16,800 






13 


30 






16,800 




Acute follicular. 


13 


35 


F.* 




16,300 






14 


30 


F. 


4,750,000 


16,000 


80 


Temperature 101°. 



1 Zeitschrift f. Heilkunde, 1883, p. 198. 

2Prag. med. Woch., 1890, p. 303. 

3 Pee: Inaug. Dissert., Berlin, 1890, p. 8. 



GRIPPE. 



229 



Table XVII. — Tonsillitis {Continued). 



z 


Age. 


X 

(U 

t» 


Red cells. 


White 
cells. 


hgemo- 
globin. 


Remarks. 


15 


27 


M. 




15,500 


67 


Six days; slight. 


16 


32 






15,000 




17 


Adult. 


F. 


4,860,000 


14,000 




Follicular. 


18 


30 


M. 


4,730,000 


13,500 


76 


Convalescent. 


19 


24 


F. 


5,000,000 


13,500 


68 


Follicular. 


20 


Adult. 


M. 


13,500 






21 


24 






13,300 






22 


36 






13,200 




Follicular. 


23 




M. 


4, 952, 000 


12,250 


94 




24 


24 


F. 


5,816,000 


11,900 


65 


Streptococcus; slight articu- 














lar rheumatism. 


25 




M. 


5,000,000 


11,800 


90 


Follicular. 


26 


19 


F. 


4,552,000 


11,600 


52 




27 


18 


M. 


5,150,000 


11,500 


83 


Chronic recurrent, out in two 


28 


26 






11,000 




days. 


29 


23 






10,900 


68 


Follicular. 


30 


22 


F.' 


5,016,000 


9,600 






31 


23 


F. 


7,925 


52 


Follicular; slight; tempera- 














ture 99^" next day. 


32 


34 






7,700 




Bronchitis. 


33 


45 


F.' 




6,800 






34 


Adult. 




4,200,000 


5,800 


60 


Follicular, 



The blood examination has no diagnostic value so far as I am 
aware. It is worth knowing that a simple tonsillitis can cause leu- 
cocytosis, to the end that if such is discovered on blood examination 
we need not suppose that some other process is present to account 
for the increase. 

GRIPPE. 

" Grippe " is a term very loosely used to designate any infec- 
tion of relatively short course, especially if catarrhal symptoms are 
present. Seldom is the diagnosis established by satisfactory bac- 
teriological evidence. In all probability, therefore, many of the 
cases included in the table below are not true " influenza. " 

The references to the hsematology of the disease in literature are 
very scanty. Orion (Archiv. d. Med. milit., 1890, p. 280) found 
fibrin increased during the early days of the disease. Eieder 
{Munch, med. Woch., 1892, XXXIX.) found no leucocytosis in 
grippe and but little in the "catarrhal pneumonia" following it 
(Ttirck). 

The following table shows that the leucocytes are normal in 
about two-thirds of the cases. Sixty-five of the two hundred and 



230 



SPECIAL PATHOLOGY OF THE BLOOD. 



fourteen cases showed leucocytosis, but in several of these some 
complication was very possibly present. The absence of leucocy- 
tosis is of importance in excluding pneumonia and local inflammatory 
conditions. The leucocyte count does not help us to distinguish 
the disease from typlioid. In this decision the serum reaction is our 
mainstay (see below, p. 458). From malaria it may be distinguished 
by the absence of malarial organisms. In one case after an opera- 
tion for traumatic epilepsy, the temperature rose to 104°, with a chill, 
and the question of meningitis was considered. The absence of leu- 
cocytosis excluded the meningitis, and the attack turned out to be 
grippe, which was just then very prevalent. 

Table XVIII.— Grippe. 
White cells. 

Between 2,000 and 3,000= 2 cases. 



3,000 " 


4,000 = 


5 




4,000 " 


5,000 = 


13 




5,000 " 


6,000 = 


15 




6,000 " 


7,000 = 


37 




7,000 " 


8,000 = 


16 




8,000 " 


9,000 : 


16 




9,000 " 


10,000 = 


22 




10,000 " 


11,000 = 


23 




11,000 " 


12,000 = 


17 




12,000 " 


14,000 = 


21 


u 


14,000 " 


15,000 = 


10 




15,000 " 


16,000 = 


8 


(( 


16,000 " 


17,000 = 


4 




19,000 " 


20,000 = 


4 




20,000 " 


21,000 = 


1 




Total cases = 


214 





Red cells. 

Between 3,000,000 and 4; 000, 000 
4,000,000 " 5,000,000 
5,000,000 " 6,000,000 

25 cases. 

SEPTICEMIA. 

Puerperal septicaemia, infected wounds, septic arthritis, septic 
endocarditis, general infections with pyogenic bacteria, "pyaemia," 
are all identical so far as their effects on the blood are concerned, 
and will be considered together under the general head of Septi- 
caemia. 



= 2 cases. 
= 9 " 
= 14 " 



SEPTICAEMIA. 



231 



Bacteriology of the Blood. 

Cocci can be demonstrated in cultures from the blood of septi- 
caemia more frequently than in any other class of infections. Eo- 
senbach ' in 1884 found streptococci and staphylococci in sepsis. 

Garre ^ in 1885 found the last-named coccus in a case of osteo- 
myelitis. In 1890 V. Eiselsberg^ found staphylococci in ten cases 
of septic wounds and one case of osteomyelitis, and streptococci and 
staphylococci together in five more patients whose wounds had be- 
come septic. 

Czerniewsky/ Stern, and Hirschler^ found the same organisms 
in puerperal fever, the former observer in five cases. 

Brunner,*^ Hoff," and Blum** found pyogenic staphylococci in 
pyaemia and sepsis, and Saenger,^ Eoux and Lannois,'" Cantu,^' 
and Bommers'"' had equal success, each in a single case. 

Canon'^ and Sittnian'" investigated large numbers of cases with 
many positive results, and Grawitz'^ and Petruschky'^ and Cohn^' 
were successful in finding pyogenic cocci in the blood of cases of 
ulcerative endocarditis as well as in other septic infections. Her- 
schlaff^^ found them in erysipelas, acute tuberculosis, perforated 
typhoid ulcer, etc. Ktihnau, on the other hand, was unable to find 
anything in the blood of twenty-three severe pysemic cases, and was 
successful in only one out of twelve cases of ulcerative endocarditis. 

Taking the results of all these investigators together, it seems 
evident that in some cases of septicaemia, blood cultures, taken 
according to the directions on page 47, show the presence of pyo- 
genic organisms, and that in obscure septic cases the diagno- 
sis may be greatly facilitated by such an examination. Negative 
results are of course very far from excluding septicaemia, but posi- 
tive ones are sometimes of great value if proper precautions are 
taken in the technique of the examination. In the diagnosis of 

^ " Microorganismen b. d. Wundinfectionskrankbeiten, " etc. Wiesbaden, 1884. 
^Fortsch. d. Med., 1885, No. 6. Rif. Med., 1892, No. 96. 

sWien.klin. Woch., 1890, No. 30. I'-^Deut. med. Woch., 1893, No. 16. 

^Archiv f. Gynakol., 1888, No. 33. '^T>evit. Zeit. f. Chirurg., 1893, p. 571. 

5 Wien. med. Presse, 1888, No. 28. ^^J)eut. Arch. f. klin. Med., 1894, p. 573. 
^Wien. klin. Woch., 1891, No. 20. Charite-Annalen, 1804, vol. x. 

'Dissert., Strassburg, 1890. ^^Zeii. f. Hygiene, 1894, pp. 59 and 413. 

sMlinch. med.' Woch., 1893, No. 16. '^Deut. med. Woch., 1897, No. 9. 

9Deut. med. Woch., 1889, No. 8. i^Sem. Med., 1897, p. 105. 

^« Revue de Med., 1890, No. 12. ^^Oeut. med. Woch., 1897, No. 25. 



232 



SPECIAL PATHOLOGY OF THE BLOOD. 



malignant endocarditis, often a most difficult one, Grawitz thinks 
blood cultures are especially important and likely to prove positive 
when the disease is present (see Diseases of the Heart, p. 316). 

Almost all observers agree that the finding of pyogenic cocci 
(except the staphylococcus albus) in the blood makes the prognosis 
almost surely fatal. The toxicity of the blood is doubled. 

Red Cells. — All observers agree that very marked anaemia is 
present in severe cases. Eed marrow post mortem I have seen in 
two instances. Eoscher's' investigations tend to show that the 
diminution in red cells in septicaemia is greater than in any other 
infective disease, and appears in a shorter time. He found such a 
diminution present no longer than a few hours from the beginning 
of the illness. He finds the amount of anaemia proportional to the 
severity of the case, and (reckoning by means of the estimated solid 
residue) concludes that whenever the blood has lost one -quarter of its 
substance or more, death follows. He considers, therefore, that help 
as to prognosis is given us by the blood examination in septicaemia. 

The serum becomes very watery, partaking of the general atro- 
phy of the blood tissue. In a case of intensely acute puerperal 
sepsis Grawitz found the red cells reduced to 300,000 ( !) although 
the patient had been sick less than twenty-four hours. The case 
seems almost incredible, but is reported in great detail in the au- 
thor's recent text-book, to which reference has so frequently been 
made. He accounts for it by the combination of blood destruction 
and dilution. 

In seventeen cases of puerperal sepsis seen at the Massachusetts 
General Hospital in recent years the red cells averaged 3,800,000, 
which is very low, considering the shortness of the illness in most 
cases. (The influence of hemorrhage during parturition must of 
course be taken into account.) 

In most of the septic wounds which I have seen the counts have 
not been low. But in one case of septicaemia from a suppurating 
fibroid of the uterus the red cells numbered only 1,800,000. Sw- 
ing reports a septic endometritis with 1,600,000 red cells. In a 
case of puerperal sepsis of only a few days' duration, in a woman 
not previous anaemic, Hayem^ recently reports the following figures : 
December 3d —Red cells 1,450,000 



White cells . 
Haemoglobin, 



7,500 



20 per cent. 



'Inaug. Dissert., Berlin, 1894. ^La Med. Moderne, January 13th, 1897. 



SEPTICEMIA. 



233 



December 6tli— Red cells. 2,578,000 

White cel-ls 8,000 

Haemoglobin 40 per cent. 

December 24tli— Red cells 4,231,000 

White cells 7,200 

Haemoglobin 65 per cent. 

(Recovery.) 



Such cases are the best examples we have of an acute ancemia 
(hemorrhage excepted). 

The hcemoglohin is usually diminished about as much as are the 
corpuscles. Nucleated red cells are very often seen ; whether or not 
they have prognostic value cannot yet be stated. In differential 
diagnosis their presence helps us to exclude typhoid and miliary 
tuberculosis, in which diseases they rarely are found. 

Deformities in the shape and size of the corpuscles are not usu- 
ally marked except in the severest cases. Ewing has noted a reduc- 
tion in the diameter of the cells in anaemic cases. 



Table XIX. — Puerperal Septicemia. 



Sex. 



Red cells. 



31 
21 
29 



28 



F. 



25 
34 



2,300,000 
3,900,000 



3,784,000 



White cells. 



77, 500 
26,000 
23, 900 
21,000 
9,500 
15,500 

15,000 
11,800 
22,000 

13,600 

8,300 

15,800 

14,900 

15,000 

9,500 

20,800 
15,900 
35,600 
33,000 
35, 600 



Per cent 
haemo- 
globin. 



68 



55 



55 



Remarks. 



Autopsy. 

Two days before delivery. 

Day of delivery. 

One day after delivery. 

Five days after delivery; 

breasts caked. 
Ten days after delivery. 
Twenty-six days after delivery. 
Miscarriage five days before ; 

septic ; curetted. 
Three days later, temperature 

falling. 

Seven days later, temperature 
normal. 

Fourteen days later, tempera- 
ture up ; curetted again. 

Fifteen days later, temperature 
falling. 

Sixteen days later, temperature 
falling. 

Thirty-two days later, temper- 
ature falling. 

September 2d, 1897. 
September 9th, chills. 
September 13th. 
September 16th. Recovered. 



234 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XIX. — Puerperal Septic.eml\ {Continued). 



6 


Affe. 


Sex. 


Red cells. 


White cells. 


Per cent : 
ha?uio- 
globin. 1 


7 


25 


F. 


2,936,000 


20.000 




50 










21.000 




8 


32 


F. 


4.904.000 


19.300 












9.300 




9 


24 


F. 


3,556.000 


18.400 




10 




F. 




Marked 












increase. 




11 


26 


F. 


5,368,000 


5.600 




12 


24 




3,428,000 


33,500 


45 








28.800 




13 


19 




3.536,000 


9,600 












6,800 






oq 




J. -ton 000 


1-L =^00 


'±0 










13,400 












7.400 












17.500 












12.200 












9.300 




15 


26 




4,056,000 


12,400 


30 










14.800 












18.400 




16 


27 






12.200 












8.200 












11,400 




17 


40 






9,200 





Remarks. 



April 1st. 1894. 
April 3, 1894. 
Curetted. 

One week later, well. 

Polymorplionuclear cells, 94,^^; 

lymphocytes. 6j?. 
Died. 

Witli general peritonitis. 

Secondary operation. 

July 18th. Peh ic cellulitis. Diff. 
count 500 cells (chlorosis). 
Polynuclear. 73,^^ ; lympho- 
cytes (s.), 22 : 13'mp'hocytes 
(L). 4 : eosinophiles, 15?. Reds 
slight irregularity in size and 
shape. Xo nucleated reds seen. 

July 29th. 

May 2d. With toxic nephritis. 

^lay 9th. 

May 14th. 

May 24th. 

May 28th. 

Jime 3d. 

June 8tli. Secondary anaemia. 
Polynuclear, 86.6^ : lympho- 
cj'tes (s.), 9.4^ : lymphocytes 
(1.), S% ; eosinophiles. .8^: my- 
elocytes. .2^c. Reds stain 
palely in centres, moderate 
poikilocytosis and irregularity 
in size. Normoblasts. 1. 

June 14th. 

June 28th. 

December 5th. 

December 9th. 

December lltli. died. P.. 140- 
170 : T.. 103 -105 -~ : R., 35-60. 
T. 104\ Recoyered. 



Table XX., A. — Septic "Woui?ds. 



Red cells. 



White 
cells. 



Per cent 
haemo- 
globin. 



Remarks. 



37 

28 
31 



27 



F. 5,880,000 
M.l 7.600,000 
F. 5,680,000 



15,840,000 
M.j 4,450, 000 
M. 5,600,000 



48.400 
25.400 
15, 300 

23. 200 
10,500 



8,800 ! jSeptic finger 



Sloughing breast ; bedsore. 
Septic wound of foot. 
Sloughing breast after cancer 

operation. 
One month later ; wound clean. 
Septic hand. 



SEPTICEMIA. 



235 



Table XX., B. — Septicemia with Arthritis. 





Age. 


QJ 
W 


Red cells. 


White 
cells. 


haemo- 
globin. 


Remarks. 


1 


8 


M. 




25,000 




Pus in elbow joint ; no injury. 










43,000 




Two days after operation, vent 














not free ; opened further. 










24,000 




Seven days after operation. 










20,700 




Eight days after operation. 










6,700 




Sixteen daj^s after, well. 


2 


21 






23,800 




T. lor. 


3 


34 


M. 




19,000 




Gonorrhoea! pus in knee. 


4 


59 


M. 


4,520,000 


18,500 




Pus in shoulder joint ; no trauma. 


5 


28 






18,200 




T. 99'. 


6 


22 






17,500 


72 


Gonorrhoea and syphilis. 


7 


55 






17,500 




Gonorrhoeal. 


8 


9 






17,100 




Gonorrhoeal. 


9 


28 






16,500 




Gonorrhaal. 


10 


42 






14,100 


50 


Gonorrhoeal. 


11 


22 






13,800 




Gonorrhoeal ankle. 


12 


16 






13,300 


52 


Gonorrhoeal. 


13 


32 




3,864,666 


12,500 




T. 99°. Gonorrhoeal. 


14 


32 






12,200 




T. 102 \ Gonorrhoeal. 


15 


33 






11,900 




Gonorrhoeal. 


16 


32 






9,700 




T. 101°. Gonorrhoeal. 


17 


21 






9,400 




Gonorrhoeal. 


18 


28 






9,100 




Gonorrhoeal. 


19 


28 






9,000 




Gonorrhoeal. 


20 


39 


ii. 




8,940 




Ankle gonorrhoeal. Cultures neg- 














ative. 


21 


? 






8,800 


76 


Gonorrhoeal. 


22 


32 






6,200 




T. 101°. Gonorrhoeal. 


23 


21 






6,200 




Gonorrhoeal. 



Table XX., C. — General Septicemia. 



Age. 



Red cells. 



White 
cells. 



Per cent 
haemo- 
globin. 



Remarks. 



Adult. 



22 



44 



43 
20 
11 



5,248,000 
1,800,000 

3,776,000 



41.400 
46,000 

25,800 

20,700 
30,700 

12,100 
27,000 
10,800 
13,000 
18,600 
19,400 
13,200 
12,200 



52 



Suppurating fibroid. Strepto- 
coccus. 

A fatal case, yet no fever .' Strep- 
tococcus. 
Cholangitis. 

Pus in eye and throat. Strepto- 
coccus."^ 
Cause? 

Septic leg, pus burrowing. 
December 15th. 
December 17th. 
December 19th. 
December 20th. 
December 21st. 
December 23d. 



236 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XX., C. — General Skfticjemix {Continued). 



6 


Age, 


x' 

<v 

CO 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 










12,400 




December 26tli. 










10,400 




December 28th. 










11,000 




January 5th. 










22,000 




January 15th. 










34,000 




January 19th. Autopsy. 


8 


33 






24,000 


75 


April 24th. 










19,400 




April 26th. 










18,000 




May 1st. 










19,600 




May 3d. 










43,200 




May 11th. T. 104f^ No au- 














topsy. 


9 


55 






10,100 




Pneumococci in blood. Autopsy. 


10 


33 




4,160,666 


22,000 


45 


Multiple septic embolism. Sugar 














in urine. 










16,000 




Tenth day. 










22,000 




Seyenteenth day. Autopsy. 


11 


38 






19,800 




First day. 










29,100 




Third day. 










27,200 




Fourth day. 










25,200 




Sixth day. 



Hmmoglohincemia with reddish staining of the serum is often 
noticeable in the dried and stained cover-glass specimen when the 
plasma is deeply stained. 

Leucocytes. — Considerable controversy has taken place as to the 
changes in the white cells effected by septicaemia; some observers 
finding leucocyi:osis, wdiile others find none. 

The results of experimental infections referred to above (see p. 
110) and the parallelism of the leucocyte changes in pneumonia, 
peritonitis, and diphtheria fully explain these apparent divergences, 
which perfectly exemplify the rules stated on p. 105. 

Leucocytosis occurs only when the struggle between the patient 
and his disease is intense, and w^hichever is victorious. AYhen 
either side wins without any difficulty, i.e., in the mildest and in 
the severest cases, leucocj^osis is nearly or entirely absent: indeed, 
leucopenia may be found (as for instance in a case of septic endo- 
metritis reported by v. Limbeck— only 3,000 leucocytes). Von 
Limbeck and Krebs' found no leucocytosis in cases of puerperal 
septicaemia, but these were all fatal cases or very mild ones. Rie- 
der, on the other hand, and the great majority of other observers 
(Sadler,^ Roscher,' Kanthak,' Grawitz, etc.) find leucocytosis. This 

^Krebs: Dissert., Berlin, 1893. sRoscher: Dissert., Berlin, 1894. 

2 Sadler: Loc. cit. -iKanthak: Brit. Med. Journal, Jun^, 1892. 



9 



SEPTICEMIA. 237 

means that in most cases observed by these writers the infection 
was of moderate severity. Swing's experience leads him to the 
conchision that while the rule that suppuration produces leucocy- 
tosis is almost invariable, it must be remembered that leucocytosis 
may promptly disappear when exudation ceases, and that suppura- 
tion involving mucous surfaces may induce very slight leucocytosis. 

Only 14 of the 56 cases in Tables XIX. and XX. showed no 
leucocytosis. One was very mild, the other proved fatal on the day 
of the count. The leucocytosis is of the ordinary polynuclear type 
wdth disappearance of eosinophiles and diminution of lymphocytes. 
Myelocytes and " stimulation forms " are usually present in small 
numbers. The reappearance of the eosinophiles seems to me to 
have some favorable prognostic significance. 

Summary. 

1. Eapid development of severe anaemia. 

2. Leucocytosis marked, except in very mild or very severe 
cases. 

3. Blood cultures may contain pyogenic cocci. 

Diagnostic Value. 

The advantage of a positive bacteriological examination is ob- 
vious. Of the value of the blood count in distinguishing septic from 
non-septic wounds and estimating the degree of sepsis and the im- 
portance or needlessness of operative interference, not much is 
known. The subject deserves to be carefully worked out from a 
surgical point of view. The following cases, however, tend to show 
that we might utilize blood counting far more than we do to deter- 
mine questions of this sort : 

Case I. — Frank B suffering with appendicitis was operated 

on by Dr. M. H. Eichardson at the end of an attack. A little pus 
was found, the appendix was excised, and the wound nearly closed, 
a small strand of gauze, however, being left in. Several days after 
the operation, there being at the time no external discharge, the 
temperature rose. The wound seemed perfectly clean. The man 
was very nervous about himself, and much stirred up at each dress- 
ing; and as the temperature never went higher than 101°, there 
seemed to be considerable doubt as to what the cause of the elevated 
temperature was. The blood count in this case showed 52,000 leu- 
cocytes. On opening the wound a large amount of broken-down 
blood clot was evacuated, and the temperature came down to normal. 



238 SPECIAL PATHOLOGY OF THE BLOOD. 

Case II. — Mrs. S had a pus tube shelled out and the ab- 
dominal wall was sewed up tight. Ten days after the operation the 
temperature began to look as if pus were present. Here again the 
patient was exceedingly nervous; and, as so often happens, the 
question was asked and re-asked, whether she was keeping up her 
own temperature by the state of her mind. The blood count, how- 
ever, showed marked leucocytosis, which led to a careful ether ex- 
amination, revealing a fluctuating mass behind the uterus, from 
which pus was obtained by puncture. 

Case III. — Mr. E entered the Massachusetts General Hos- 
pital in December, under the service of Dr. C. B. Porter, with a 
compound fracture of the thigh. Some days after it had been put 
up, the temperature began to suggest the presence of pus, the 
wound, however, remaining perfectly clean. I counted the blood, 
and found a marked leucocytosis. A more thorough exploration of 
the wound revealed a pocket of pus, the evacuation of which brought 
down the temperature. I was not sure in this case whether the 
absorption of the blood clot, such as takes place, I suppose, after 
any compound fracture, would be sufiicient to cause leucocytosis. I 
therefore counted several cases in which there was fever and pre- 
sumably blood-clot absorption, namely, a hsemothorax, a pelvic 
hsematocele, two compound fractures, and a crushed foot; in none 
of these was any leucocytosis present. 

Case TV. — Mr. S was operated on by Dr. J. C. AYarren for 

traumatic epilepsy. Nothing special was found, and the wound 
was closed. Ten days after the operation the temperature rose to 
104°, and the patient complained of severe headache and pain in 
the back. I counted the blood, and found no leucocytosis. Next 
day the temperature was down. The patient apparently had the 
grippe. 

Several cases in which an old malaria was supposed to be 
" brought out " by a surgical operation, the patient having irregular 
fever and chills after the operation, have shown, on examination of 
the blood by the writer, no malarial organisms but marked leuco- 
cytosis. In these cases the symptoms of "malaria" ceased when 
the wound was more thoroughly drained, and I have no doubt that 
many cases of " malaria " after surgical operations are really wound 
sepsis. 

It is difficult to make inferences from a leucocytosis in such 
cases, because no one, so far as I know, has thoroughly investigated 
the blood condition during the normal healing process of wounds. 
But there are certainly many cases in which we need the kind of 
information about the condition of a wound which the blood might 
give us, if the changes in connection with wounds were better known. 



ABSCESS. 



239 



How often the questions are asked : Is this patient septic? Does 
this temperature mean anything of importance? Is this wound well 
drained? Is this complaint of pain hysterical or does it mean some- 
thing operable? 

How often the blood count would help us to answer such ques- 
tions without leaving it for time to settle them after the most urgent 
need of settling them is gone, we do not yet know. 

In puerperal cases, the fact that leucocytosis is always present 
for several days after delivery makes it harder to judge from the 
blood whether a given case is septic. I doubt if the blood count 
will give any information on this point not to be more easily ob- 
tained in other ways. Blood cultures, if positive, are of far greater 
importance, but take more time. 

ABSCESS. 
lodophilia. 

Goldberger and Weiss^ have recently applied the iodine reaction 
originally described by Ehrlich and Gabritschowsky to the study of 
the polynuclear leucocytes of the blood in cases of local suppuration. 
A syrupy mixture of the following elements is made : 

lodi sublim 1 

Pot. iodidi 3 

Aq. dest 100 

Acacia ad syrupum. 

This is painted on a slide and the unstained cover-glass prepara- 
tion is pressed down into it. So treated normal blood or that of non- 
suppurative diseases shows the following : red cells dark yellow ; 
white cells light yelloiv with very refractile, citron yellow nuclei. 

In purulent affections the protoplasm of the leucocytes stains 
hroivn, either diffusely or in a granular or network distribution. 

Kammier"^ distinguishes three stages in the appearance of the re- 
action : 

(«) A slight diffuse brownish discoloration of the protoplasm. 

(h) A concentration of the brown color into intensely stained 
flakes and granules. (This is the type most often seen.) 

(c) An intense brown discoloration of the whole protoplasm. 

Czerny, and recently Hofbauer, have found iodophilia in cases 
of grave anaemia, primary or secondary. In chlorosis and the 

1 Wien. klin. Woch., 1897, No. 25. 
2Deut. med. Woch., April 3d, 1899. 



240 



SPECIAL PATHOLOGY OF THE BLOOD. 



milder types of secondary anaemia it is not present unless there is 
pus somewhere in the system. Leucaemia usually shows a posi- 
tive iodine reaction both in the polynuclear leucocytes and in ex- 
tracellular flakes. Hodgkin's disease, on the other hand, shows 
no such reaction. In purpura, contusions, and hsematoma, the ex- 
tracellular flakes reacting to iodine are abundant. 

After an abscess is opened the brown color is at first confined to 
the periphery of the cell and soon disappears altogether. " Cold " 
abscesses, no matter how large, do not produce the reaction, but 
acute felons with only a thimbleful of pus have shown marked 
iodine reaction. 

Leucocytosis due to non-infective agents {e.g., spermin) is not 
associated with any such reaction. On the other hand, it is not 
peculiar to infections which produce pus. In pneumonia, in puer- 
peral sepsis without localization, and in non-suppurative terminal 
infections a well-marked iodophilia may occur. 

It has also been found in cases of fracture and after severe con- 
tusions or prolonged narcosis. 

Other Effect of Abscess on the Blood. 

The effects of abscess upon the blood are, I suppose, due to sep- 
ticaemia. Nevertheless septicaemia tvith abscess formation differs 
enough from septicaemia without abscess formation, both clinically 
and haematologically, to make a separate description convenient. 

The most easily studied variety of abscess is that connected 
with appendicitis, inasmuch as the frequency of operations in such 
cases gives us opportunity to verify what we suppose to be indicated 
by the blood count and see how far our suppositions are true. 

At the Massachusetts General Hospital, most patients with other 
varieties of abscess go straight to the surgeon and their blood is not 
examined, but many cases of appendicitis come first to the medical 
wards, and hence we have records of over eighty cases whose blood 
has been examined. 

I shall therefore begin the description of the blood in abscess by 
an account of appendicitis, which may probably be considered a 
typical case of abscess formation. 

APPENDICITIS. 

After excluding all cases in which the diagnosis was not sure we 
have left seventy-two cases. 



APPENDICITIS. 



241 



Table XXI.— Appendicitis. 



50 



35 



19 31 M. 



3,400,000 
6,800,000 



5,184,000 
4,800,000 
4,390,000 
6,000,000 
6.500,000 
5,072,000 



5,200,000 
5,144,000 



16 



52,000 
43,000 
39,900 
36.800 
36,000 
35,000 
84,000 
34,000 
28,000 
24,200 

16,850 
15,600 
10,700 
15,100 
14,600 
11,800 
17,850 
18,200 
13,100 

24,000 

12,500 
19,500 
24,000 
23,000 
16,100 
22,500 
13,000 

9,500 
22,300 

9,500 
22,000 
19,400 
14,900 
21,900 

21,700 
21,400 
16,000 
24,400 
20,200 
47,700 
16,700 
13,000 
10,700 
30,300 
20,900 
17,700 
25,100 
28,100 
20,400 
15,400 
25,000 
11,900 
15,600 
21,900 
19,000 
11,900 
12,800 
11,700 
12,300 
15,600 
13,400 
14,700 
16,500 
11,300 
20,540 




S 2.9 



Remarks. 



Question of typhoid; pus found at operation. 
Chronic case; 96 per cent, of adult leucocytes. 



Three days after operation. 
Seven " " " 

Second attack; operation at 11 p.m. November 5th, 

count at 5:30. 
Serous peritonitis found. November 6th, 5 p.m. 
November 7th, 3 p.m. 

8th, 4 " 

Temperature still up. November 9th, 5 p. M. 
November 10th, 5: 30 p.m. 

11th, 8:30 " 
12th, 8:30 " 
13th, 8 a.m. 
" 13th, 8: 30 p.m. 
Recovery complete ten days later. 
24° September 1st; operation, free turbid fluid without 

adhesions. 
September 10th. 

" 12th ; pocket of pus found. 

January 14th. 

" 15th; before operation, |v. -fpus. 
Not operated; entrance. 
Second day. 
Third 

12: 20 operated; belly full of pus. 
8 : 30 moribund ; blood dark and hard to get. 
July 6th. 
" 8th. 

" 10th, T. 104° : recovery. 
Appendicitis eight to nine days; operation; post-caecal 

abscess. 
November 5th, first operation. 
10th. 
13th. 
15th. 
16th. 

" 19th, second operation (pus pocket). 

20th. 
21st. 
22d. 

" 26th, third operation (pus pocket). 
27th. 
28th. 
29th. 
30th. 

December 1st. 

2d. 

3d. 

4th. 

5th. 

6th. 

7th. 

8th. 

9th. 
10th. 
11th. 
12th. 
13th. 
21st. 
25th. 
26th 
October 5th. 



242 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table XXI. — APPE^-DICITIS ( Con tin ued). 



Remarks. 



27' 

2- 5S, 
29 -JO M. 
3n 14 31. 

31 

32 25 M. 



38 25 M. 

34 

35 40 F. 



33,000 
14,640 
9,200 
21,000 
24,900 
13,700 



4.800.000 
5,564.000 
4,670.000 
5.296,000 



4,680,000 
4,688,000 



5.120,000 
5,660,000 



6,160.000 



3.300.000 
4,380.000 



4.330.000 
5.910.000 



4,250,000 



4,950.000 
5,000.0X1 
4,626.000 



20.100 
14,000 
12,400 
13,250 
8,750 
9,600 
20,000 
19,000 
20,000 
9,000 
10,000 
20,000 
20.000 
19,750 
15,000 
19,600 
12.000 
8,933 
19.500 
19.000 
18,930 
IS.OOO 
17.500 
16,250 
17.450 
12,000 
16,200 
16,200 
16.051 
16,000 
8.000 
7,500 
6.800 
16.000 
16.000 
S.OOO 
7..500 
6.60O 
16,000 
15,600 
19,500 

22,900 
35,300 
32,800 
15,523 
15,330 
14,800 
10.000 
14, 700 

14,700 
13.150 
14,400 
10, .300 

I4.nnn 
13.400 
11.2iXi 
13.00-11 
l3.rHX 

17. (KM I 

12.0CHJ 



resistant belly. 



not operated, 
liquids every two hours. 



October 6th. 
8th. 

" 9th ; moved bowels. 
12th : tender still and tense. 
99° to 100' temperature. 
Normal: still sore. 
Appendicitis twenty-four hours 
October 2:3d. 

24th. 9 A. M. 

24th. 4 P.M. 
: " 24th. 11 p. M 
I " 25th. 8 A.M. 

25th, 3 p. M. 
'May 24th. 
I " 25th. 

June 5th; temperature. 101.4°: pain and romiting. 
June 7th: no pain. 

" 8th : no pain ; temperature, 100.6° ; discharged. 
Operated; pus. 

January 13th. 
j " 15th. 
I " 29th. 
February 1st. 

5th; after operation. 
No operation. 
Purulent peritonitis. 



Accident case: operation: pint of pus under pressure. 

Fifth day. November 7th. 
November 8th. 

j 11th; not operated: well on 17th. 

Eighth day; operation; large abscess cavity. 

Operated. 

Entrance. 

Same evening; no operation. 
.Next day. 

General peritonitis, 
November 12th. noon. 

:2th. 8: 30 p.m. 
" 13th. 8 a.m.; not operated. 

13th, 6 P.M. 

March 25th, 9 p.m. ; vomiting, pain, tenderness. 

27th: comfortable, no vomiting; signs more 
localized. 
" 28th ; slight tenderness only. 
" 29th ; bowels move well; no symTDtoms. 
" 30th; operation; large amount of pus. 



20th ; general peritonitis. 
21st : 

Five days : third attack; operation; 
I no perforation: prompt recovery. 
27th. 8 P.M. 

28th ; symptoms less ; no operation. 
Februarv 23d. 



free turbid fluid, 



24th. r - P^^- 



Catarrhal. 

,3 P.M. , November 9th: appen-licitis twenty-four hours. 
5 P.M.. November lOth; temperature. 98.8=. 

IVisible tumor. March 27th. 

April 26th, operated; pus. 



APPENDICITIS. 
Table XXI. — Appendicitis {Continued). 



243 



51 



c o c 



Kemarks. 



61 

62 
63 

64 24 



4,860,000 



4,664,000 



3,690,000 
5,600,000 



5,106,000 
5,600,000 
6,500,000 
6,500,000 

6,000,000 



12,000 

16,900 
11,900 

11,800 

19,900 

11,700 
17,600 
16,670 
11,950 
10,800 
10,875 
21,000 

10 700 
9,000 

10,500 
10,400 
9,800 
10,400 
10,500 
10,140 

10,040 
9,000 
8,400 

10,000 
7,200 
7,600 
7,760 
7,600 
7,600 
7,6G0 
7.050 
7,000 
6,600 
6,000 



58 



4,320,000 



Appendicitis cake. August 3d, operation; gangrenous 
I appendix witli adhesions. 
August 6th, faecal fistula. 

No symptoms except pain for twenty-four hours; not 
operated. 

Very shght tenderness; no resistance or dulness. 
July 6th. 

Temperature up: tenderness and resistance. July 7th, 

operation ; pus found. 
December 28th, 4 p.m. 

30th, 10 A.M. 
31st, 11 " 
January 1st, 9 p.m. 
5th. 

July 27th; nine days pain and vomiting. 

July 28th; more pain, tenderness and vomiting; opera- 
tion showed pus. 

November 7th, appendicitis six days. 

Operation: abscess with considerable pus; gangrenous 
perforated appendix with concretion in it. 

Not operated till later. 

February 6th. 12 m.; slight pain and tenderness. 

" 7th, 3 P.M. ; temperature dropping. 
Catarrhal. 

One week, fourth attack; no cake, no acute symptoms; 

operation : no pus. 
Sixth day, operation: abscess, |i. pus. 
Operated; no pus; catarrhal. 
December 1st. 

6th. 
15th. 
16th. 

No pus. 

No operation. 
No pus. 

Catarrhal appendix; five days in hospital 
Catarrhal appendix. 

chronic; nearly well; operation; no pus. 
" or very slight. 



From the seventy-two cases of the adjoining table, together with 
ninety-four other counts not here recorded, the following conclu- 
sions are to be drawn : 

1. Red cells : no changes except in chronic cases with long- 
standing abscess. 

2. Coagulation often slow, but fibrin always increased in sup- 
purating cases. 

3. As in most infections the mildest and the severest cases show 
no leucocytosis. Six cases with general j^i^i'ideut peritonitis showed 
no leucocytosis, its absence being confirmed by repeated examina- 
tions. The total absence of leucocytosis in a case not obviously 
mild is a very bad prognostic sign as in pneumonia and diphtheria. 



244 



SPECIAL PATHOLOGY OF THE BLOOD. 



4. Catarrhal a2)penclicitis is rarely accompanied by leucocytosis 
(only once in this series — 14,000). 

5. An increasing leucocytosis means a spreadiiig jjrocess and may 
he the only evidence of the fact. In Case 40 of this series, the jja- 
tient entered with vomiting, localized ^^ain and tenderness. The 
leucocytosis was 15,600. Three days later he was comfortable, had 
no vomiting and very little tenderness, and in all respects seemed 
to be improving, yet the white cells had risen to 22,900. Opera- 
tion was postponed owing to the lack of all unfavorable symptoms 
except the blood count. Next day the bowels were moving well and 
the patient had no fever and no had symptoms of any kind, but his 
leucocytes had risen to 35,300. On the following morning the sur- 
geon was finally persuaded to operate and found a large amount of 
pus. 

A steadily increasing leucocytosis is always a bad sign and 
should never be disregarded even when (as in this case) other bad 
symptoms are absent. It is of far more significance than a larger 
count which does not increase. 

6. The size of the leucocytosis is of comparatively little signifi- 
cance. A low count (8,000-11,000) means one of three things : 

(«) A mild case. 

(h) A very severe case. 

(c) An abscess thoroughly walled off. 

After the abscess has ceased to spread and has become well 
walled off, the leucocyte count remains stationary or decreases. 
If it bursts into the general peritoneal cavity the count may rise 
sharply or it may fall to normal or subnormal, its movement de- 
pending on the degree of resistance which the system offers. 

7. In the majority of cases the pus' is neither completely walled 
off nor free in the belly, and such cases are accompanied by a mod- 
erate and fluctuating leucocytosis, which rises and falls according to 
a variety of conditions which cannot be accurately interpreted. 

It usually increases in the first three or four days of the illness, 
and then becomes stationary or declines if the case is taking a favor- 
able course {i.e., if the j)us is being absorbed or walled off), while 
it continues to increase when the case is going on from bad to worse. 

Case 20 illustrates the course of the leucocytes in a favorable 
case not operated on ; the leucocytes fell gradually but steadily from 
hour to hour so that in two days the count came down from 20, 100 
to 8,750, the tumor and tenderness simultaneously disappeared, and 



APPENDICITIS. 



245 



the patient was well in a few clays more. Case 38 dropped in eight 
hours from 16,000 to 8,000 and quickly recovered. In Case 19, the 
leucocytosis fell in three days from 33,000 to 9,200, but rose again 
when the bowels were moved by enema, and took some days to reach 
normal again. Evidently the peristalsis injured the abscess wall so 
that the process began to spread again and had to be walled off 
afresh. 

8. When a leucocytosis of 18,000-25,000 is maintained for a 
number of days it usually means a large abscess pretty well walled 
off. 

9. The majority of cases as seen at the Massachusetts General 
Hospital on the second, third, and fourth days of the illness showed 
leucocytosis of 15,000-24,000, thirty-three of the present series fall- 
ing within these figures. Counts larger than this have always been 
proved to mean a large amount of pus or a general peritonitis. Of 
the cases below 15,000 (fifteen in all) twelve did not come to oper- 
ation, or if operated showed no pus. This statement excludes the 
four cases of general purulent peritonitis without leucocytosis men- 
tioned above. 

10. Case 18 illustrates several points. After the first operation 
the leucocyte count did not fall so rapidly as usual, and the cause 
of this soon turned out to be a pus pocket, after the evacuation of 
which the count fell in twenty-four hours from 47,700 to 16,700, 
only to rise again for another accumulation of the same kind. 

After this last (third) operation the case progressed slowly but 
favorably, and yet the leucocyte count remained more or less above 
normal for a month. The wound was healthy ^ freely discharging, 
and had healed satisfactorily at the time of the last count recorded. 

Hubbard, in a study of the counts recorded in the aurgical wards 
of the Massachusetts General Hospital, concludes that while the 
leucocyte count may be of value in distinguishing appendicitis from 
other non- suppurative affections, it is of little value (when the diag- 
nosis of appendicitis is established) in helping us to predict the 
further course of the case, or in guiding our judgment regarding the 
time to operate. 

Bloodgood's' results may be thus summarized: 

1. Chronic cases : leucocytes subnormal with few exceptions. 

2. Acute cases at end of an attack : leucocytes, 10,000 to 15,000. 

3. Early acute cases: leucocytes, 8,000 to 22,000. 

' Medical Record, October 20th. 1900. 



246 



SPECIAL PATHOLOGY OF THE BLOOD. 



4. Gangrenous appendicitis : leucocytes, 13,000 to 25,000. 

5. Appendix full of pus : leucocytes, 15,000 to 35,000. 

6. Appendix with, abscess : leucoc}i;es, 6,000 to 60,000. 

7. In acute cases, if operation is delayed, the leucocytes rise 
^ith. an increase of other symptoms. A rising leucoc^-te count is a 
symptom of danger. 

8. In cases giving a history- of appendicitis and a high leuco- 
cytosis, but without local signs, one may feel reasonably sure that 
a deep abscess exists. 

9. With, a leucocyte count of over 20,000 no time should be lost 
before operating. 

Differential Diagnosis. 

1. The presence of a marked leucocj-tosis excludes simple colic 
witli or without cojistijxdion, and excludes certain forms of intestinal 
obstruction (if uncomplicated). Such cases of intestinal obstruc- 
tion as are complicated with ulceration or gangrene or due to cancer 
may raise the leucocyte count. 

Between general peritonitis from an appendicitis and intestinal 
obstruction, the presence of marked leucocytosis points to the 
former ; but its absence may accompany either affection. I remem- 
ber a case in which, the diagnosis lay between these two affections, 
and operation was delayed because th.e absence of any leucocytosis 
was thought to rule out peritonitis, and it was hoped to get the 
bowels started by enemata, etc. 'VMien finally the abdomen was 
opened stinking pus gushed out and the patient died the same day. 

2. Treves^ has reported several cases in which it was hard to 
decide whether the diagnosis was typhoid or appendicitis. A blood 
examination would probably have decided the matter, as it has in 
three cases in the writer's experience. Most cases of appendicitis 
of any severity show leucocytosis; typhoid almost never does if 
uncomplicated. Curtis- reports a case of typhoid with a tumor and 
tenderness in the right iliac region which closely simulated appen- 
dicitis but turned out to be a floating kidney. The blood count 
would have decided the matter. 

3. Between axjpendicitis and pus tube the blood gives no help, 
as both affect it alike. 

4. Ovarian or pelvic neuralgia (uncomplicated) never causes leu- 

' ^[edico-Chirurgical Transactions, 1888, Ixxi., p. 165. 

2 " Twentieth Century Practice of Medicine," vol. viii., p. 461. 



APPENDICITIS. 



247 



cocytosis and may be excluded by its presence. The same is true 
of floating kidney, which has been sometimes confounded with ap- 
pendicitis. 

5. Gall-stone colic, and I'ciial colic if uncomplicated by inflamma- 
tory disturbance, cause no leucocytosis, and can therefore be distin- 
guished from appendicitis in most cases. If cholangitis, cholecys- 
titis, pyelitis, or severe cystitis complicate the colic, the examination 
of the blood will be no help to us. 

6. Impaction offceces in the csecum will not cause any leucocy- 
tosis and may be excluded when such is present. The count may 
be of use, it seems to me, in deciding us whether an enema ought 
to be given. It is sometimes desirable to give an enema in cases 
simulating appendicitis, to help clear up the diagnosis, but some 
physicians are afraid to do so for fear of causing a walled-off ab- 
scess to break into the general peritoneal cavity. In such cases, if 
no leucocytosis were present, we might go ahead with a clearer con- 
science. 

Mr. B entered the Massachusetts General Hospital Septem- 
ber 20th, 1893, with a diagnosis of appendicitis. For twenty days 
he had been having pain and tenderness in the region of the appen- 
dix, pain being controlled by morphine. The bowels had been 
loose, he said. There were dulness, tenderness, and a distinct tumor 
in the region of the appendix, with slight pyrexia. The blood count 
showed only 8,000 leucocytes. He was given a compound cathar- 
tic pill, had a large movement of the bowels, and all symptoms and 
signs disappeared. 

7. Extra-uterine pregnancy and pelvic hsematocele may cause 
leucocytosis like appendicitis, but do not increase fibrin unless peri- 
tonitis is present, and are likely to shoiv a marked diminution in red 
corpuscles if the hemorrhage is severe. The red cells are normal in 
appendicitis except in chronic cases with abscess. 

8. Floating kidney has been already mentioned in Curtis' case, in 
which in combination with typhoid it closely resembled appendicitis. 
Even without the presence of typhoid, the same difficulty of diag- 
nosis may arise between appendix and floating kidney. The pres- 
ence of leucocytosis could not be accounted for by the latter. 

One of the next most common forms of abscess seen in medical 
wards is pyosalpinx, which I shall call by the English name of 
"pus tube." As this produces the same effect on the blood as pel- 
vic abscess or pelvic peritonitis, I shall consider the three processes 
together. 



248 



SPECIAL PATHOLOGY OF THE BLOOD. 



PUS TUBE, PELVIC ABSCESS, AND PELVIC PERITONITIS. 

Almost all that has been said of appendicitis applies equally 
well to these conditions. 

Table XXII., A.— Pus Tube and Pelvic Abscess. 




Remarks. 



Double pus tube ; too weak to operate. December 15th. 
December 22d. 

December 29th ; abscess burst per vaginam. 
January 4th, abscess opened in groin. 
8th. 
11th. 
Pelvic abscess. 
Pus tube. June 18th. 
June 19th. 
20th. 

27th, fever and vomiting just before catamenia 
July 1st, temperature normal. 
" 8th, mass decreasing. 
" 14th, slight thickening still. 
Pus tube; septic arthritis; jaundice. 
Pus tube. 
Double pus tube. 
General purulent peritonitis. 
Pus tubes. 

Double pus tube. November 17th. 
November 19th, operated. 
Pus tubes. 
Pus tube. 

Pus tube four weeks' duration. 
Pus tube. 

Pelvic abscess (fetid pus). 
Pus tube. 
Pus tube. 

Pus tube ; operation ; pus found. 
Pus tube operated. 
May 1st. 

" 11th, mass the same; pus tube. 
Pus tube. 
Pus tube. 
Pus tube. 
No fever. 
May 4th. 

" 9th. 
No fever. 

May 18th, flow of pus from os started by manipulation. 
Out doors. 

Pus tube and ovaritis; operation; pelvis full of foul 

pus; recovery after hysterectomy. 
Pus tubes. 
" tube. 

" tube; three hours after food. 
" tubes. 
" tube. 
" tube, etc. 

" tube; svphihs. October 7th. 
October 12th. 
Pus ear. 
Pus tube. 

Pus tube. May 8th. 
May 18th, transferred. 
Pus tube ; large amount of pus found. 
Pelvic peritonitis. 



Temperature 99° 
May 2d. 



April 26th. 



PUS TUBE, PELVIC ABSCESS, ETC. 
Table XXII. — Pus Tube and Pelvic A.'b^cis.^^ {Continued). 



249 



36 



37 20 

38 38 



40 1 85 



21 



24 



3,696,000 



4,310,000 
3,008,000 
4,700,000 



3,910,000 
4,756,000 

4,240,009 



3,800,000 
7.000,000 
4,125,000 



472,000 
5,840,000 



14,975 
12,600 

14,800 
13,853 
12,500 
12,200 
12,200 
12,300 
12.000 
11,850 
13.750 
11,000 
10,600 
11,000 
11,500 
10.400 
10,000 
10,000 
17,000 
13,400 
9,000 
9,200 
7,500 
7,200 



Remarks. 



Pus-tube. July 21st, chills and delirium. 
July 23d. 

" 25th; operated. 
Pus tube; chlorosis. 
Pus tube. 

Pus tube (double) ; operated. 
Pus tube; slight. 
Pus tube. June 2d. 
June 10th. 
Pus tube. 

Pus tube. January 5th and 6th. 

Pus tube. Not operated; very slight. 
Chronic salpingitis. June 21st. 
June 25th, better. 

' 29th. 
Pelvic peritonitis. 
Pelvic abscess (?). 
Pelvic abscess. August 28th. 
September 3d, temperature up. 

" 6th, normal temperature. 
Salpingitis, 9 a.m. ; T. 99.4°. 
4: 15 P.M. ; five days in hospital. 
Pus tubes (small; size of finger). 
Pus tube. 



From these data together with two hundred and nineteen other 
counts not here recorded I conclude that : Increasing counts of leu- 
cocytes usually point to the need of an operation ; stationary leuco- 
cytosis to a well walled-off abscess. The size of the count is a rough 
measure of the size of the abscess, and patients without leucocytosis 
rarely need operation and usually recover under palliative treatment, 
as also do many ivith leucocytosis. 

Differential Diag7iosis. 

Pelvic pain and soreness may be as great in various non-suppu- 
rative conditions (ovarian neuralgia, etc.) as when abscess is present, 
but the leucocyte count is raised in none of the pelvic disorders of 
women except abscess, septicaemia (puerperal, after abortion, etc.), 
and hemorrhage (meiiorrhagia, metrorrhagia, ruptured tubal preg- 
nancy). Endometritis and cystitis usually cause no leucocytosis. 
The application of these rules will not infrequently help in the 
diagnosis of pelvic disease and in deciding how much importance to 
attach to the complaints of pain, tenderness, etc., in a doubtful case. 
The absence of leucocytosis makes us rightly confident that no ab- 
scess of any considerable size exists. 



250 



SPECIAL PATHOLOGY OF THE BLOOD. 



OTITIS MEDIA. 

Most cases, if purulent, show leucocytosis both before and after 
paracentesis. If serous (see Table XXIII., cases 7, 14, 15, 17, 18, 
19) the count is usually lower, and we can predict with moderate 
certainty whether serum or pus will be found on puncturing the 
drum. When the mastoid is involved the count runs higher. If 
the case drags on, the haemoglobin may get low, otherwise the red 
cells are not affected. 



Table XXIII. — Otitis Media. 



d 
2; 


Age. 


X 

<D 
OC 


Red cells. 


White 
cells. 


Per cent 

llSBIllO- 

globin . 


Remarks. 


1 


6 


F. 




36,700 




Nephritis acuta. April 30th. 










27,300 




May 7th. 










34,400 




May 14tli, otitis only. 










27,000 




May 22d. 










21,000 




May 28th, slight discharge still. 


2 


2 


M. 




23,000 


55 


3 


19 






21,900 




Ninth, T. 103.6°. 










13,200 




Eleventh, T. 101°. 










10,800 




Fourteenth, T. 99°. 


A 


a 
o 


M 
IVi. 




1 ft Ann 




5 


20 






17,000 




With jugular thrombosis. 










21,900 




Third day. 


6 


45 


M. 




14,500 




With cerebral abscess. 


7 


Adult. 


M. 


4,786,000 


16,800 




Serous. 


8 


47 


F. 


4,168,000 


16,600 


65 


Double purulent ; vent not free ; 












mastoid sore. 


9 


19 


F. 


5,120,000 


16,480 


88 


April 28th. 








8,800 


49 


May 5th, well. 


10 


27' 






15,800 




11 


Adult. 


F. 


5,"942,000 


15,200 




Pus. 


12 




F. 


4,472,000 


14,750 


60 


December 7th, hysteria. 








5,416,000 


9,750 


46 


December 25th (during dyspnceic 














and cyanotic attack). 


13 


9 






13,900 






14 


32 






12,000 




Serous. 


15 


24 




4,472,000 


11,200 


20 


Serous. 


16 


22 




11,000 






17 


27 


F. 


4,850,000 


8,500 


69 


Serous. 


18 


7 


F. 


4,416,000 


6,400 




Catarrhal. 


19 


Adult. 


F. 


4,100,000 


4,000 




Serous. 


20 


4 


M. 


Marked 




Purulent ; chronic right, acute 










leuco- 




left. Diff. 116 cells ; polymor- 










cytosis. 




phonuclear cells, 57^ ; lympho- 














cytes, 31 ; eosinophiles, 3. 



In some cases the blood alone enables us to distinguish otitis 
and its effects from typhoid. In a case recently examined which 



OSTEOMYELITIS. 



251 



several excellent clinicians pronounced typhoid, though there was a 
marked leucocytosis and no serum reaction, the autopsy showed pus 
in the jugular and lateral sinus but no typhoid. 

OSTEOMYELITIS. 

In four cases in which no external opening was present, the 
patient complaining only of pain in the bone, the counts of leuco- 
cytes were 29,600, 25,600, 24,310, and 18,000; in each the predic- 
tion that pus would be found was verified at operation. Three 
differential counts in chronic cases with sinuses showed nothing re- 
markable, no increase of eosinophiles and no myelocytes. 

The diagnostic value of the blood in osteomyelitis seems to me 
considerable, inasmuch as it is difficult by the symptoms alone to 
feel sure enough of the existence of pus to be willing to operate. 
"Rheumatic pains," "growing pains," and neuralgia can be ex- 
cluded by the presence of leucocytosis. 

Other Abscesses. 

(1) Felon. — It is striking to see how small a collection of pus 
can raise the leucocyte count. Patients with felons containing less 
than one -half drachm of pus may have a leucocytosis of 15,000 to 
22,000. I have counted the blood in three such cases. The element 
of septicaemia must be considerable. It seems to make no difference 
whether or not the pus is under great tension. The leucocyte count 
does not fall sharply after the felon is opened, but gradually dimin- 
ishes during the next seven to ten days. Even a 

(2) Gum boil raised the white cells to 27,000 in one case. An 

(3) Abscess of the vulva showed 23,500 leucocytes per cubic mil- 
limetre, and an 

(4) Abscess o f the vagina, 12,800. Other varieties are : 

(5) Parotid abscess, 45,500 leucocytes per cubic millimetre. 

(6) Sub2)ectoral abscess, 16,000 leucocytes per cubic millimetre. 

(7) Abscess of the neck, 22,200 leucocytes per cubic millimetre. 
Carbuncle, 41,000 leucocytes per cubic millimetre. 

(8) Psoas abscess (infected), 50,000 leucocytes per cubic milli- 
metre. 

(9) Abscess of ovary, 26,000 leucocytes per cubic millimetre. 

(10) One Q,2i^Q oi iDerinephritic was watched for some days 
while the patient was getting up strength for an operation. It was 



252 



SPECIAL PATHOLOGY OF THE BLOOD. 



an abscess of several months' standing, not increasing in size during 
tlie last montti, and the counts, as we should expect, did not rise 
or fall considerably but showed a steady well-marked leucocytosis. 

July 29th, white cells, 21,400 



" 30th, 
August 8th, 
11th, 
" 24th, 



21,200 
22,400 
23,000 

22,200. (Operation.) 



A second case counted showed only 16,000. Both abscesses con- 
tained over a quart of pus. 

A third case, evidently tuberculous in origin and probably not 
much infected with pyogenic cocci, showed only 10,000 white cells 
per cubic millimetre. 

(11) Abscess of the Lung. — Five cases following pneumonia have 
occurred at the Massachusetts General Hospital within the last 
three years; the counts were as follows: Case I., 16,800; Case II., 
16,000; Case III., 16,400; Case IV., 30,000; Case V., 5,100. 

(12) Subphrenic abscess, four cases. 



Case. 



Red cells. 



White cells. 



Per cent 
haemoglobin. 



Remarks. 



4,450,000 



3,200,000 



53, 267 
25, 600 
15, 500 
17, 600 
22,000 
15,300 

13,800 
16,600 
18,000 
22, 500 



55 



Mav 16th. 
May 17th. 
May 20th. 

October 20th. Supposed typhoid 

for first week. 
October 23d. 
October 27th. 
November 5th. 

November 10th. Operation; a 
quart of pus ; recovery. 



Diagnostic Value. 

1. The patient with vulvar abscess was so morbidly modest that 
she complained of all parts of her body except the one diseased, and 
gave a train of symptoms which failed to account for the leucocy- 
tosis. The presence of this leucocytosis called for a much more 
searching physical examination than would have otherwise been 
made, and the seat of real trouble was discovered. 

2. {a) The diagnosis between perinephritic abscess and cyst of 



YELLOW FEVER. 



253 



the kidney is materially assisted by the fact that the former causes 
leucocytosis, while the latter (see page 335) does not. 

(b) Both cancer of the kidney and perinephritic abscess cause 
leucocytosis, but if fibrin is not increased cancer is the more likely 
of the two. This differential mark has served me well in two cases. 

(c) Hydatid of the kidney and pyonephrosis are not to be dis- 
tinguished from perinephritic abscess by the blood examination. In 
abscess of the lung the blood gives no information that cannot be 
more easily gained in other ways. 

3. Subphrenic abscess may be confounded with malignant dis- 
ease, both of which may cause leucocytosis ; but the absence of any 
increase of fibrin speaks against the existence of an abscess. 

GONOERHCEA. 

The red cells are not affected, but in acute cases a moderate leu- 
cocytosis is present and fibrin is increased. Qualitatively, the white 
cells have been said by Neusser and others to show an increased 
percentage of eosinophiles corresponding to the large proportion of 
these cells in the urethral discharge. Vorbach has carefully studied 
twenty cases with reference to this point and finds the eosinophiles 
in the blood to vary from 0.5 to 11.5 per cent — averaging 4.2 per 
cent — within normal limits. Bettman found the eosinophiles usu- 
ally increased, especially when the posterior urethra was involved. 
In one case with epididymitis the eosinophiles numbered 25 per 
cent.^ 

YELLOW FEVER. 

Jones^ found coagulation slow, the red cells not much dimin- 
ished but showing decided degenerative changes ; hsemoglobinsemia 
is common. He makes no observations as to the white corpuscles. 
Pothier of New Orleans, studying the epidemic of 1897, found the 
following results in 154 cases. The red cells were never consider- 
ably diminished. The leucocytes varied from 4,600 to 20,000 — 
averaging about 9,000— haemoglobin usually diminished at the 
height of the disease 50 to 75 per cent. Normoblasts were noted 
in a few specimens. 

A case recently observed at the Massachusetts General Hospital 
showed two days before death 7,800 leucocytes, 92 per cent of hsemo- 

^ Archives for Derm, and Syphil., vol. 49. 

Journal of the American Medical Association, March 16th, 1895. 



254 



SPECIAL PATHOLOGY OF THE BLOOD. 



globin, with an absence of the typhoid serum reaction. Through the 
kindness of Dr. Pothier I have been able to study cover slips 
from twelve cases of yellow fever from the Charity Hospital of 
New Orleans. The differential counts of leucocytes are as follows : 





I. 


II. 


III. 


IV. 


V. 


VI. 


VII. 


VIII. 


IX. 


X. 


XI. 


xn. 


Polymorphonuclear 


neutro- 






























77 


74 


93 


86 


87 


88 


97 


84 


86 


84 




73 


Small lymphocytes. . 




18 


22 


15 


11 


8 


4 


3 


5 


4 


6 


4 


20 


Large lymphocytes . 




5 


2 


2 


a 


5 


8 




11 


10 


6 


18 


6 








2 




.5 














1 


1 


Myelocytes 








.5 












*4 





Eed cells showed nothing except in Case VIII., in which there 
were marked deformities and a few normoblasts. In some cases 
there was a marked leucocytosis, in others none. (For serum reac- 
tions, see page 458). 



TYPHUS FEVER. 



Ewing' in four cases found no leucocytosis. Tumas'^ found no 
leucocytosis^ as the following case shows : 



Date. 


Day of 
disease. 


Temperature. 


Red cells. 


Per cent 
haemoglobin. 


White cells. 












A.M. 


P.M. 








January 


4th 


4th. 




40.0 


















5th 


5th. 


39.2 


39.6 


4,440,000 


80 


9,600 


u 


6th 


6th. 


39.0 


39.5 


4,220,000 


77 


4,800 


u 


7th 


7th. 


39.0 


40.0 




M 


8th 


8th. 


39.2 


39.3 


4,280,000 


77 


3,200 


U 


9th 


9th. 


39.0 


39.5 




tt 


10th 


10th. 


38.8 


39.2 


4,440,000 


77 


3,200 


« 


11th 


11th. 


38.3 


39.3 






<{ 


12th 


12th. 


39.0 


39.2 


4,380,000 


80 


1.600 


M 


13th 


13th. 


38.8 


39.5 


4,780,000 


80 


3,200 


U 


14th 


14th. 


38.7 


39.0 




U 


15th 


15th. 


38.0 


38.7 


4, 960,000 


80 


1,600 


M 


16th 


16th. 


38.1 


38.8 






(( 


17th 


17th. 


38.7 


38.6 


4,160,000 


70 


4,800 


(( 


18th 


18th. 


37.7 


38.2 




(C 


19th 


19th. 


36.6 


38.5 


3,820,000 


67 


1,600 


U 


20th 


20th. 


38.1 


38.3 






<t 


21st 


21st. 


37.5 


38.1 


3,450.000 


63 


3,280 


tt 


22d 


22d. 


38.1 


37.8 


3,450,000 


60 


3,200 


it 


23d 


23d. 


37.5 


38.0 




i( 


24th 


24th. 


37.4 


38.0 


3,130,000 


60 


3,200 


t( 


25th 


25th. 


37.4 


39.3 






u 


26th 


26th. 


39.2 










Died on the 26th. 











' Ewing : New York Medical Journal, December 16th, 1893. 
■^Arch. f. khn. Med., vol. xK., p. 363. 



THE BUBONIC PLAGUE. 



255 



On the other handy Everard and Demoor/ and Wilks^ found 
leucocytosis. 

MALTA FEVER. 

According to the article in Allbutt's recent "Text-book of Med- 
icine " the red cells fall gradually in the course of the fever from 
5,000,000 to about 3,500,000. Bruce finds the leucocytes normal 
in most cases. (See also page 466.) Charles^ makes the amazing 
assertion that at the height of the fever polymorphonuclear neutro- 
philes are entirely absent from the blood and only lymphocytes to 
be found. Musser and Sailer report a prolonged case with no im- 
portant changes in the blood. The serum reaction with the Bacillus 
melitensis has been obtained in cases of Malta fever by Musser, by 
Cox, by Curry (18 cases), and in Osier's clinic. 

GLANDERS. 

Christol and Kiener* reported leucocytosis in glanders. In a fatal 
case of acute glanders with autopsy which was recently studied at 
the Massachusetts General Hospital the following counts were re- 
corded : 

October 24th, 1897. Leucocytes, 13,600; haemoglobin, 100 per cent. 
October 31st, 1897. Leucocytes, 11,600. 
November 4th, 1897. Leucocytes, 13,000. 
November 9th, 1897. Leucocytes, 12,600. 
November 12th, 1897. Leucocytes, 12,400. 

Serum reaction absent; fibrin increased; pure culture of glanders bacilli 
from abscesses; 86 per cent of the leucocytes were polymorphonuclear; eosino- 
philes absent. 

The bacilli of glanders can occasionally be cultivated from the 
blood. 

THE BUBONIC PLAGUE. 

In 1895 Aoyoma, a Japanese observer, studied the blood of this 
disease.^ He found the bacilli peculiar to the disease by cover-slip 

^ Annales de ITnstitut Pasteur, February, 1893. 

2 Ref . in Sajous' Annual, 1895. 

3 Lancet, July 30th, 1898. 

^ Comptes Rendus de TAcad. des Sciences, November 23d, 1868. 
5 " Mittheilungen aus d. Med. Fac. d. Kaiserlich Japanischen Universitat, " 
viA. iii., No. 2. Tokyo, Japan, 1895. 



256 



SPECIAL PATHOLOGY OF THE BLOOD. 



preparations from the blood. The red corxmscles were not altered 
except that their number per cubic millimetre was at times increased 
(e.g., 7,600,000, 8,190,000). The cause of this I do not know, but 
it accounts for part of the leucocytosis. The white corpuscles showed 
a marked increase— 20,000 to 200,000 (!) per cubic millimetre. 
This leucocytosis was made up almost wholly of polymorphonuclear 
leucocytes ; the eosinophiles were markedly diminished, and the blood 
plates were increased. The Austrian Plague Commission found 
only a moderate leucocytosis in most cases. 



ACTmOMYCOSIS. 

Ewing (loc. cit.) reports leucocytosis (21,500) in a single case 
affecting the lungs, and Schmidt gives the following : 



Date. 


Ked cells. 


White cells. 


Per cent 
haemoglobin. 


October 6th 




12,000 
14,500 
19,700 
22,900 
18,900 


35 

38 
23 


15th 


3,1TO,000 


20th ; 


26tli 


3,200,000 
2,550,000 







In two cases of actinomycosis occurring at the Massachusetts Gen- 
eral Hospital the following counts were recorded : 



Case. 


Location of the disease. 


Leucocytes. 


Remarks. 


1 


Liver 


31,700 
28,400 
28,200 
20,900 
23,000 


June 18th, 1897. 
" 19th. 

" 25th. Autopsy. 
April, 1897. 

August, 1899. Autopsy. 


2 









EPIDEMIC DROPSY. 

(Acute Anaemic Dropsy.) 

MacLeod, in Vol. III. of Allbutt's "System of Medicine, de- 
scribes under this title a disease not uncommon in India and other 
tropical countries. The blood shows a marked and constant anaemia 
with leucocytosis and an " increase of granular or molecular matter 
in the serum.'' Dr. Green, of the United States Marine Hospital 
service, recently wrote me an account of two cases strongly resem- 



RELAPSING FEVER. 



257 



bling MacLeod's description of epidemic dropsy; these cases were 
observed by Dr. Greene at Key West, Fla. One was fatal and. the 
other ended in recovery. The blood of both cases was notable in 
that the corpuscles were almost invariably oval instead of round, re- 
minding him of the blood of amphibia. He was good enough to 



t 




Fig. 33.— Blood in Epidemic Dropsy. Note oval s<hape of corpuscles. Magnified 350 

diameters. 

send me preparations of the blood ; a microphotograph of one of 
them is here reproduced. E-ouleaux formation was absent, another 
point in common with amphibian blood. There was no apparent in- 
crease of the leucocytes when I saw the blood, late in the conva- 
lescence of the second case. (On the significance of oval forms, 
see p. 85.) 

TETANUS. 

In two (fatal) cases of tetanus treated with antitoxin, I observed 
the following counts : 

White cells. Haemoglobin. 

Case I. June 21st, 1897 11,100 70 per cent. 

June 23d, 1897 . ..• 11.900 

" II. 19,600 

The eosinophiles do not decrease as in most fevers. 
17 



258 



SPECIAL PATHOLOGY OF THE BLOOD. 



BERI-BERI. 

In a single afebrile case seen at the Massachusetts General 
Hospital the following is recorded: Ked cells, 3,896,000 ; white 
cells, 7,800; haemoglobin, 48 per cent. 

The eosinophiles are said to be much increased in the acute 
stages. Spencer' states there is no leucocytosis. Ewing and Daubler, 
each in 3 cases, found normal leucocyte counts with moderate anae- 
mia and no eosinophilia. 

RELAPSING FEVER. 
(See page 422.) 

(a) Diagnosis. Leucocytosis is the rule. It is most marked 
just after the crisis. In countries where this disease is common 
che difficulty in diagnosing cases between attacks (when the spiro- 
chaetes are absent from the blood) is frequently met with. Lowen- 
thal has perfected a method by which in most cases the diagno- 
sis can be made by means of the effect of the serum of suspected 
cases on the spirochaetes of other active cases. The organism 
cannot be cultivated as yet, so that a diagnosis of this kind is pos- 
sible only during epidemics Avhen fresh blood containing the organ- 
ism can be obtained. A drop of blood from the suspected case is 
mixed with a drop from a patient then undergoing a paroxysm, 
and the two are sealed with Avax between slide and cover-glass 
and left in the thermostat for half an hour together with a mix- 
ture of normal blood and blood containing spirochaetes as a con- 
trol. At the end of that time, if the case be one of relapsing fever, 
the organisms in contact with the blood from that case cease their 
motion, while those in the control are lively. It is not a clump re- 
action but a direct bactericidal effect which persists in the serum 
nearly up to the time of the next attack. The diagnosis so made by 
Lowenthal in forty cases was verified in every case by the course of 
the disease. In this way mild or abortive cases with few organisms 
in the blood can also be identified. 

(h) Prognosis. If the above bactericidal power lasts as late as 
the seventh day from the last attack, and in sufficient intensity to 
immobilize the spirochaetes in one hour or less, there will be no re- 
lapse. If these conditions are not fulfilled, relapse is sure to fol- 
low unless prevented by treatment. Lowenthal has verified this 
prognostic use of the serum in over one hundred cases. 

1 Lancet, January 2d, 1897. 



CHAPTER V. 



DISEASES AFFECTING THE SEROUS MEMBRANES. 

Tuberculous affections of serous membranes have been dealt 
with elsewhere (p. 280) ; but an exception was there made of pleu- 
risy, for although there is reason to believe that the majority of cases 
of serous pleurisy are due to tuberculosis, we rarely have proof of it, 
and most observations upon the blood of pleurisy have not been 
accompanied by bacteriological examination of the effusion. Tu- 
berculous cases have not always been distinguished from non-tuber- 
culous. Hence the two are necessarily considered together here. 

SEROUS PLEURISY. 

Von Limbeck finds in non-tuberculous cases from 13,000 to 15,000 
leucocytes per cubic millimetre. The red cells and haemoglobin are 
not much affected except in chronic cases. 

Rieder finds in non-tuberculous cases during the stage of fever 
moderate leucocytosis, 13,000 in one case in which the bacteriolog- 
ical examination showed the presence of Fraenkel's diplococcus in 
the exudation. After ihe fever has subsided the leucocytosis falls 
to, or nearly to, normal, so that cases examined for the first time 
some weeks after onset would show no increase at all. This he 
thinks explains the results of Halla and others who found no leuco- 
cytosis in serous pleurisy. According to Rieder the presence or ab- 
sence of leucocytosis depends not so much on whether the product is 
serum or pus as on whether the trouble is stationary or advancing. 

In tuberculous pleurisy despite fever Rieder found but 4,600 white 
cells in one case, and Pick got similar results in two cases. 

Hayem makes no clear distinction of tuberculous and non-tuber- 
culous cases, and states that " acute inflammatory " pleurisy has from 
7,500 to 12,000 leucocytes per cubic millimetre. The fibrin network 
is much less dense than in pneumonia; in most of the tuberculous 
cases it is not increased at all. 

Morse reports 224 counts in 20 cases of serous pleurisy— 9 of 



260 



SPECIAL PATHOLOGY OF THE BLOOD. 



tliem tuberculous. No relation could be established between the 
number of leucocytes and the presence, absence, or degree of fever, 
the presence of blood or microscopic pus in the fluid, the amount 
of fluid or the duration of the illness. Increase or decrease in the 
amount of fluid was not accompanied by any parallel change in the 
circulating leucocv^es. 

Only 10 of the 224 counts were over 11,000, and 9 of these 10 were 
in a single case which was shown at autopsy to be complicated by a 
secondary pneumococcus infection. Morse concludes that primary 
serous pleurisy does not show a leucocytosis. His figures are as 



follows : 

FroDi 8,000 to 4,000 2 cases. 

4.000 " 5,000 19 " 

5,000 6,000 40 

6,000 " 7,000 31 • 

7,000 " 8,000 50 " 

8,000 " 9,000 42 " 

9,000 " 10,000 27 " 

" 10,000 " 11,000 8 " 

" 11,000 " 12,000 4 " 

" 13.000 " 14.000 1 " 

Total 224 cases. 



The following chart (Morse) shows how " the white count dodges 
up and down without the slightest apparent connection with the quan- 
tity of fluid." 

In 242 cases examined at the Massachusetts General Hospital 
the count of leucocytes was : 

Table XXIV.— Pleuritic Effusion (Serous). 



Between 3,000 and 4.000 4 cases. 

4,000 " 5,000 11 " 

5,000 " 6,000 30 " 

6,000 " 7,000 29 " 

7,000 8,000 26 " 

8,000 " 9,000 40 " 

9,000 " 10,000 29 " 

10,000 " 11,000 27 " 

. " 11,000 " 12,000 11 " 

12,000 " 15,000 25 " 

Over 15,000 10 " 

Total 242 cases. 

Average = 6,130. 



SEROUS PLEURISY. 



261 



Here tuberculous and non-tuberculous cases are not distinguished, 
and a majority of them were not seen till the trouble had been 
going on two or three weeks. The patients did not seek advice until 
the effusion was large enough to cause dyspnoea. Of the 242 cases 
all but 35 had no leu- 
cocijtosis. Most of the 
cases were afebrile or 
nearly so. Eight cases 
reacted to injections 
of tuberculin. N'one 
of these eight had leu- 
cocytosis. 

The cases ivith leu- 
cocytosis were mostly 
those seen in the fe- 
brile stage, near the 
beginning of the sick- 
ness. No differential 
counts were made. 

In chronic cases 
the red cells are said 
to be considerably di- 
minished, but this has 
not been the case in 
our series : no count of 
under 4,000,000 was recorded, and the coloring matter was not 
much diminished. 

Summary. 

1. Eed cells and haemoglobin show no important changes. 

2. In adults the white cells are probably never steadily increased 
as a result of simple uncomplicated serous pleurisy. Occasional _ 
waves of leucocytosis occur in a small percentage of cases, but even 
then the leucocyte count rarely reaches 14,000. Continuous leuco- 
cytosis indicates some complication. 

Diagnostic Value. 

The blood count may help a good deal in doubtful cases by ex- 
cluding empyema, pneumonia, and malignant disease of the lung, 
all of which are accompanied by high leucocyte counts. Compare 
the average count in serous pleurisy, 6,130, with the average in pneu. 



DAYS OF 
MONTH 






















DAYS OF 
DISEASE 




13 


14 


1!) 


16 


17 




19 


20 


21 


105° 

103° 
102° 
lOf 
100° 
99° 

NORMAL 




E. 




E. 








E. 




E. 




E. 




E. 








E. 




E. 




10000 




§ 




o 

o 




7200 




0089 




8000 




7200 




§ 

00 




1 




6400 1 
















































\ 








A 




























A 


J 




i 




\j 




V 










































\ 










































i 




i 










A 






































V 








TEMP. 

98' 

96° 
95° 
















o 
























erateI 




)EAStN( 








z 




o 
















z 






o 
s 

Q 












IRATIO 




NISHIN 
















OST gI 




















ASP] 


















1 


< 







FIG. 34. 



262 



SPECIAL PATHOLOGY OF THE BLOOD. 



monia, 24,000, or in empyema, 18,300. The few counts I have 
seen of malignant disease of the lung have been still higher. 

Hayem insists, rightly it seems to me, that clinicians could get 
real help from blood examination in almost every case of doubtful 
diagnosis in which the lung and pleura are in question. In children 
the leucocytes are sometimes considerably increased by even a serous 
inflammation, their blood reacting always more strongly than that 
of adults to any morbid influence, and in them it may be impossible 
to distinguish serous from purulent pleurisy. 

PURULENT PLEURISY (EMPYEMA). 



The counts in twenty-six cases observed at the Massachusetts 
Hospital are as follows : 

Table XXY. — Empyema. 





Age. 


Sex. 


Red cells. 


White 
cells. 


P^r cent 
haemo- 
globin. 


Remarks. 


1 


12 






57.800 














54,400 






2 


2 






55,000 




Streptococcus. 








5,440,000 


49,200 


51 




3 


1 






45.500 




Pneumococci in pus. 










37.700 












31.700 






4 


2 




3.032,000 


45.000 


35 












34,000 




Fifth day. 










40,000 




Eighth day. 


5 


4 






44,000 




First day. 










24,400 




Third da v. 










23.000 




Fifth day. 










20,000 




Eighth day. Tap. 










24.000 




Eleventh day. 










31.400 




Fourteenth day. 










22,000 




Seventeenth day. 










41,500 


60 


6 


20 






41,000 




February 11th. Tap. 










29,900 




February 15th. Tap. 


7 


21 






38,000 




8 


5 






37,800 






9 


32 






35,600 














35,200 






10 


4 






34,500 












6,000,000 


32.000 






11 


4 






30,400 






12 


47 






30,000 




First day. 










39,000 




Third day. 










27.000 




Sixth day. 










26,000 




Eighth day. Pneumococci in pus. 


13 


38 






30,000 





263 



Tarle XXY. — Empyema {Continued). 



6 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hcBmo- 
globln. 


Remarks. 


14 


26 






24,000 














21,000 














22,800 


45 












22,800 




June 5tli. 










34,700 




June 7th. 










29,800 




June 8th. Tapped turbid serum. 










17,700 




June 9th. 










22,000 




June 10th. 










22,100 




June 12th. 










21,800 




June 14th. 










17,200 




June 22d. 










27,300 




June 24th. 










30,100 




June 29th. 










25,800 




July 8th. 










22,600 




Pneumococcus. 


15 


6 






21.600 




Pneumococcus. 










34,500 




Five days later. 










20,600 




January 5 th. 










14,700 




January 7th. 










11,400 




January 23d. 










11,700 




January 26th. Tapped. 










18,000 




January 30th. Re-accumulation. 










26,000 




February 3d. Operated ; pneu- 














mococci and streptococci. 


16 


2 






19,600 




17 


45 






18,700 




Friedlander's bacillus. 


18 


6 






16,900 




Tap, pus. 


19 


24 




4,152,000 


15,000 


45 


Operated. 


20 


27 






14,200 




21 


39 






13,300 




Gangrene of lung also. 










14,900 




Fifth day. 










22,800 




Fifteenth day. 


22 


30 






13,000 




23 


8 






13,000 




Sterile. 


24 


22 






12,700 




Tuberculous. 








4,192,000 


10,800 


48 


December 20th. 










18,500 




December 22d. Broke into lung; 














cultures sterile. 










14,500 




January 2d. 










18,300 




January 4th. 










10,000 




January 9tli. 










16,200 


50 


Pneumococcus. 










15,500 














15,200 












4,500,000 


14,000 












4,850,000 


12,650 


85 












12,450 


60 










4,000,000 


12,000 














11,700 


44 


Cultures sterile. 










10.900 






25 


71 






8,400 




Three quarts sterile pus. 


26 


45 






7,600 




Operated ; several pints of pus ; 






6,500 




streptococci. 



264 



SPECIAL PATHOLOGY OF THE BLOOD. 



This is ill marked contrast Avitli serous pleurisy as above noted. 
Von Limbeck noticed the same thing, 

(Ewing:) "In a case of empyema, in which tubercle bacilli were 
extremely numerous, the writer found moderate intermittent leu- 
cocjirosis (maximum 18,000)." 

PERITOXITIS. 

A patient with serous pleurisy (non-tuberculous) is hardly ever in 
danger, while if the general peritoneal cavity is the seat of a like 
inflammation, recovery is almost out of the cj_uestiou. 

This clinical difference is j^arallel to the difference in the blood 
condition. Any inflammation of the peritoneum (non-tuberculous), 
whether serous or purulent, calls very large numbers of leucocytes 
into the peripheral blood. The only excei)tions to this rule are 
those cases in which the organism is so overwhelmed by the dis- 
ease that it offers no resistance. We have seen that this same effect 
is produced in the severest cases of pneumonia and diphtheria, and 
presumably it is true of many other infectious diseases in which the 
blood has been less carefully studied. 

Almost all cases of general septic peritonitis show very marked 
leucocytosis, and the spreading of a localized process is always in- 
dicated by an increasing leucocytosis. But here and there it hap- 
pens that the patient cannot react against the disease at all, and 
then the leucocytes are normal or diminished. This never occurs 
in empyema, because the system is never so overwhelmed by a sep- 
tic process in the pleura. The fibrin network is increased in almost 
all cases. The following counts, all in fatal cases, illustrate these 
points : 

Table XXYI. — General Peritonitis. 



No. 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 
2 

3 

4 

5 

6 
7 


U 
Adult. 

15 

27 

28 

27 
22 


F. 
F. 

M. 


4.860,000 
7,000,000 


54.00<.) 
32,000 

28,000 
23,000 
27,800 
23,000 
34,200 
24.100 
17.800 
24.000 
23,200 




Abscess of spleen <?). 

Puiulent : from appendix— myelocytes, 

2 per cent. 
General septic. 
Next day. 

December 6th. Epigastric. 
December llth. 
December ITtli. 

Pelvic, after abonion. Seventh. 
Fifteenth. 

Dysentery, with perforation. 
CiaMric ulcer : perforation : operation. 
Death. 


4,004.000 


6<S 
5:3 


5,317,000 


75 







PERICARDITIS WITH EFFUSION. 
Table XXVI. — General Peritonitis {ContiniiecT). 



265 



Age. 



Sex. 



Red cells. 



Adult. 

31 
Adult. 



Adult. 

53 



Adult. 
41 



4,000,000 



6,000,000 



5,760.0ri0 
6,840,000 



White 
Cells. 



22,000 
19,000 
16,000 
13,000 
25,800 
12,200 
9,000 
11,000 
8,300 
7,400 
9,700 
6,000 
6,000 
5,328 

5,300 
4,600 
Marked 
increase. 



1,700! 
2,100! 
1,600 



Per cent 
htemo- 
globin. 



Remarks. 



Chronic, purulent. 
Ruptured bladder. 
Moribund. 

First day. Rupture of gall bladder. 

Second day. Died. 

June .30th. 

July 2d. Autopsy. 

October 27th. Circumscribed. 

November 2d. 

July 19th. 

July 28th. 

Purulent ; operation. Death. 
Obstruction ; died in three days ; au- 
topsy. 

Purulent. Death within 24 hours. 

" 24 " 

After appendix operation. Dili. 1,000 
cells : Polymorphonuclear cells, 90.5 
per cent; lymphocytes, 9.5; eosino- 
philes, 0; myelocytes, 1. 

August 2d. Autopsy. 

August 3d. 

General. Gastric ulcer. 



Diagnostic Value. 

1. When a diagnosis rests between peritonitis and {a) obstruc- 
tion (non-malignant); (Jj) malignant disease; {c) hysteria, phan- 
tom tumors or malingering, the presence of marked leucocytosis with 
increase of the fibrin network speaks strongly in favor of peritonitis. 

Obstruction or malignant disease may increase the number of 
leucocytes, but rarely increases the amount of fibrin. 

Hysterical or malingering patients have normal blood. 

2. We cannot distinguish serous from purulent peritonitis in 
septic cases, hut tuherculons 2^eritonitis can always be excluded if leu- 
cocytosis is present. 

3. As to the "chronic granular peritonitis," non- tuberculous and 
non-septic, I have seen no reference in haematological literature and 
have no first-hand knowledge. 

4. In the ivorst cases leucocytosis may be absent, as in the most 
virulent type of pneumonia. 



PERICARDITIS (WITH EFFUSION). 

As in most other inflammations of serous membranes we can dis- 
tinguish the tuberculous cases which have no leucocytosis from the 
rheumatic or septic cases which always increase the white cells. 



266 



SPECIAL PATHOLOGY OF THE BLOOD. 



The tuberculous cases are discussed under tuberculosis (see p. 285). 
The following counts illustrate the rheumatic form of the disease : 



Table XXVII. 



Case 




White cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 




42,400 
33, 600 




November 8d, 1895. 






November 7th, 1895. 






19,300 




November 11th, 1895. 






17, 500 




December 8th, effusion nearly gone. 


2 


2,632,000 


21,600 


45 


December 24th, endo - pericarditis, 








chronic nephritis. 






27,100 




December 26th. 






36,600 




December 29th, no fever. 






26,700 




May 1st. 






19,200 




May 3d. 






24, 800 




May 4th. 






28,600 




May 7th. 






20,100 




May 8th. 


3 


4,568,000 


26,000 


67 


December 14th. 




19,400 




December 20th, effusion subsiding. 


4 




24, 000 






5 


4,168,000 


19,447 


67 




6 


15,400 






7 




14,600 


65 


Autopsy. 


8 




13,000 


63 


Tapped. 



Hayem has noted that pericarditis is far more apt to produce 
leucocytosis than is endocarditis. 



Diagnostic Value. 
In excluding cardiac hypertrophy or simple dilatation with rup- 
tured compensation, both of which may occasionally simulate a 
pericardial effusion, the presence of marked leucocytosis is abso- 
lutely decisive. When we are sure that eifusion exists, the absence 
of leucocytosis points strongly to a tuberculous process as its cause. 

MENINGITIS. 

Leucocytosis is usually well marked. Von Limbeck considers 
that tuberculous meningitis can be distinguished from purulent by 
the absence of leucocytosis in tuberculous cases, but Osler^ states that 
many cases of tuberculous meningitis do have leucocytosis through- 
out their course, and my own observations (see Table XXVIII.) tend 
to confirm this. Of Kieder's cases, one had leucocytosis and one did 
not. Zappert's case had 11,130 white cells, and Ziemke one with 



17,500. It seems, therefore, that we sometimes have here an ex- 
^ "Practice of Medicine," 2d edition. 




EPIDEMIC CEREBRO-SPINAL MENINGITIS. 267 



ception to the rule that tuberculous processes do not produce leuco- 
cytosis. Certainly some cases do follow this rule. But however 
this may be, it is certain that purulent meningitiSj whether second- 
ary or of unknown origin, is characterized by high leucocyte counts, 
and if in a case evidently of meningitis of some kind leucocytosis is 
absent, the case is probably tuberculous in origin. 



Table XXVIII.— Meningitis. 





Age. 


X 

OJ 
OJ 


Red cells. 


White 
cells. 


Per cent 
hasmo- 
globln. 


Remarks. 


1 


19 






62,000 




Autopsy; pneumococcus. 


2 


Adult. 


M. 


5,900*666 


40,000 




Diff. 1,000 cells: Adult cells, 93 














per cent. ; young cells, 7 ; eosin- 














ophiles, 0. 


3 




M. 


6,400,000 


33,000 




(Otitis ?) question of typhoid. 


4 


23 


M. 


6,000,000 


27,500 


95 


March 16th ; cerebro-spinal. 










16,500 




" 18th. 


5 


9 mos. 






27,000 




Tuberculous; no autopsy. 


6 


15 " 


F. 


5,020,666 


19,500 


73 


7 


7 


M. 


16,000 






8 


26 


M. 




16,000 






9 


20 


F. 




15,784 




Autopsy; cerebro-spinal. 


10 


2 


M. 




14,200 




Basilar ; no tuberculosis in family ; 














had pneumonia. 


11 


22 


M. 


4,356,000 


14,000 


72 




12 


35 


M. 




11,700 






13 


26 


M. 


5,040,000 


11,200 




Specific. 



Cerehro-spinal 7ne7iingitis (see Cases 4 and 9, Table XXVIII.) 
shows the same characteristics in the blood as do cases limited to the 
cerebral meninges. A case reported by v. Jaksch ^ had 4,800,000 
red and 24,000 white cells. 



EPIDEMIC CEREBRO-SPINAL MENINGITIS. 

Williams finds leucocytosis in about two- thirds of his cases. 

The following counts were made during the epidemic of 1897. 
The red cells are not markedly affected. Vasomotor polycythsemia 
may occur. Leucocytosis is the rule, but is not invariable. In a 
general way the higher the count the severer the case, and the 
count usually rises as the case gets worse and falls with improve- 
ment, though often very slowly. In the febrile recrudescences so 
common in chronic cases, the leucocytes usually rise again, though 
the eosinophiles may not disappear as they ordinarily do in the ear- 

iZeit. f. klin. Med., 1893, p. 187. 



268 



SPECIAL PATHOLOGY OF THE BLOOD. 



liest days of the illness. Xo in-ognostic inferences can be drawn 
frc^n the behaA'ior of the eosinoijhiles in meningitis. 

Table XXIX. — Epidemic Cerebro-Spinal Menixgitis. 



White cells. Counts. 

Between 5.000 and 10.000 9 

10.000 15.000 50 

15.000 •• 20.000 42 

20.000 25.000 27 

25.000 30.000 21 

30.000 •• 35.000 9 

35,000 " 40.000 10 

40.000 " 45.000 7 

45.000 50.000 1 

50.000 55.000 5 

Total ■ 181 counts. 



Flexner and Barker, investigating a large epidemic at Lona- 
coning, ]\Id., found leucoc^-tosis in every case (12,000-32,000 per 
cubic millimetre). The epidemic studied by AVilliams and myself 
was apparently due to the diplococcus intracellularis of Weichsel- 
bauni. Secondary meningitis (otitis media, etc.) seems to have 
similar effects on the blood. 

Diar/n osfic Value. 

Meningitis is the only intracranial disease (except abscess and 
apoplexy i which shows leucocytosis, and this fact may be of great 
help in excluding other causes of coma. 

1. Brain tumor, hysteria, lead encephalopathy, and most cases 
of narcotic or alcoholic intoxication do not cause leucocytosis and 
hence can be excluded by its presence. 

2. Uraemia, apoplexy, sun-stroke,^ diabetic coma, and post-epi- 
leptic coma may have leucocytosis and cannot be distinguished from 
meningitis when leucocytosis is present ; but the absence of leuco- 
cytosis excludes meningitis. 

3. Some cases of typhoid, when seen for the first time and with- 
out a history of the previous illness, may be diiiicult to distinguish 
fro^n meningitis, but t\'phoid never has leucocytosis if uncomplicated 
and meningitis always has. 

4. From pneumonia we cannot distingitish menmgitis by the 
blood coimt. 

^ In a case of lieat exhaustion (temperature 104' ) without coma, a leuco- 
cyte count of 2T.200 is recorded at the Massachusetts General Hospital. 



PART III. 

CHRONIC INFECTIOUS DISEASES. 



CHAPTER VI. 

TUBERCULOSIS. 
Ked Corpuscles and Hemoglobin. 

(a) Quantitative Changes. 

I. The striking fact is the absence of such anaemia as we should 
expect, judging from the i3allor of the patients and the nature of 
the disease. It is common to find a normal or even increased num- 
ber of red cells in pale cachectic-looking consumptives. We cannot 
help wondering whether our methods of examination are at fault, 
that is, whether the drop we examine is typical. (For discussion 
of the. subject see p. 72.) However this may be, it is undoubtedly 
the fact that in most cases of tuberculosis, even in advanced stages, 
the count of red cells is approximately normal. Often the hsemo- 
globin is also high. 

II. In a smaller number of cases the haemoglobin is much di- 
minished, although the count of red cells is normal — in other words, 
we find the blood characteristic of a moderately severe secondary 
anaemia. The red cells are numerous enough, but only because 
their numbers have been recruited by the influx of " half-baked " or 
decrepit corpuscles, small-sized and pale, poor in albumin and 
haemoglobin . 

The condition differs from that of chlorosis mainly in that some 
of the red cells are normally developed and nourished, while in 
chlorosis all, or nearly all, are feeble. Such blood occurs in the 
severer and more cachectic sufferers from tuberculosis, just often 
enough to make us wonder that it is not always to be found. 

III. In a small percentage of cases both red cells and haemo- 



270 



SPECIAL PATHOLOGY OF THE BLOOD. 



globin are considerably diminished, the latter usually suffering 
more than do the actual number of cells, that is, the color index is 
usually below 1. 

Von Limbeck ^ has recorded a case in which in the course of a 
tuberculous process (acute miliary) the red cells fell as low as 730,000 
(white cells, 4,300; haemoglobin, twenty-five per cent). But the 
account of the blood is not sufficiently explicit in this case to enable 
us to exclude a true pernicious ansemia in the course of which the 
tuberculosis may have been only the last incident. No other such 
case is on record, so far as I am aware. 

(Ewing :) " In phthisis as well as in other tuberculous processes, 
great caution must be used in judging of the patient's improvement 
from an increase in red cells or haemoglobin. The writer has seen the 
haemoglobin and red cells increase while the patient was rapidly los- 
ing flesh, the lesions advancing, and the total quantity of blood doubt- 
less falling. In several of Bierf reund' s cases the haemoglobin steadily 
increased while the patient was developing general tuberculosis." 

IV. Fibrin is not increased unless extensive secondary infection 
is present. 

{b) Qualitative Changes. 

I. There may be none whatever. 

II. There may be only a pallor of some of the individual cor- 
puscles with slight changes in size and shape. 

III. In very severe cases the poikilocytosis may be extreme, but 
this is much rarer than in many other cachexias of the same severity 
(e. g., malignant disease). 

IV. An important point is the usual absence of nucleated red 
cells. Even after hemorrhages it is rare to find any nucleated red 
cells, and this is in marked contrast with cancer cases, in which 
nucleated red cells are the rule. 

V. The degenerative changes described by Maragliano are some- 
times found in severe cases with mixed infection (^vide infra). 

As regards the influence of the different seats of tuberculous dis- 
ease (meningeal, pulmonary, genito-urinary, acute miliary, etc.) 
upon the red corpuscles and haemoglobin the following are the prob- 
abilities. 

Pure tuberculous disease itself, whatever its seat, has little or no 
effect upon the blood. The widely different conditions of the blood 

1 Loc. cit., p. 336. 



PHTHISIS. 



271 



found in different cases depend probably on the presence or absence 
of various other organisms (diplococcus lanceolatus, pyogenic cocci) 
associated with the tubercle bacillus, and on whether there is some 
drain on the body albuminoids (diarrhoea, peritoneal effusion, star- 
vation, prolonged suppuration). When the infection is a mixed 
one, the blood shows the ordinary effects of septicaemia (for then 
the case is practically one of septicaemia) in lessening the number 
and quality of the red cells. When there is drain on the fluids and 
proteid constituents of the body, the red cells may not seem to be 
diminished, owing to the concentration of the blood from loss of 
fluid. Under such circumstances they may even seem increased, 
but the individual corpuscles are sure to be lacking in haemoglobin 
and the other nitrogenous bodies of which they largely consist. 

Pever may be present without there being any changes in the red 
cells that we can detect. It is only septic fever, and not the fever 
of pure tuberculosis, that drains the corpuscles of their vitality and 
lowers their numbers. 

Leucocytes. 
(a) Quantitative Changes. 

Here, as with the red cells, the striking fact is the absence of 
changes in pure tuberculosis. It makes no difference whether we 
are dealing with tuberculosis of the bones, serous membranes, or 
internal organs. So long as the infection remains unmixed the 
white cells are not increased. In certain localities (lungs, kidneys) 
the opportunities for a secondary infection and septicaemia are so 
great that we frequently find evidence of it in the blood. On the 
other hand, psoas abscesses before they are opened often contain 
only tubercle bacilli, and the blood of such cases shows no consider- 
able changes. 

So much more is known of the numerical variations of the leu- 
cocytes in tuberculosis than of the other blood constituents, that I 
shall give a separate account of them in phthisis, in tuberculous bone 
disease, in tuberculous meningitis, acute miliary tuberculosis, genito- 
urinary tuberculosis, and tuberculous peritonitis. 

I. PHTHISIS. 

I. In incipient phthisis the leucocj^tes are normal except after 
haemoptysis. 

II. After attacks of hcemoptysis, there is usually leucocytosis, 



272 



SPECIAL PATHOLOGY OF THE BLOOD. 



subject to wide variations according to the amount of the hemor- 
rhage and the resisting power of the patient. 

This follows the laws of ordinary post-hemorrhagic leucocytosis 
{clde supra) and disappears quickly when the hemorrhage ceases. 

III. Cavities. — Very constantly accompanied by leucocytosis. 
Indeed the absence of leucocytosis in any case proves the absence of 
any cavity of considerable size. 

(Ewing:) "The writer has seen both lungs consolidated and 
riddled with small cavities in a case lasting five weeks, yet the leu- 
cocytes were never found above 12,000. The absence of leucocy- 
tosis in these cases of acute phthisis, which resemble pneumonia, 
may often be of value in diagnosis. Similarly in a case of subacute 
empyema in which the tubercle bacillus Avas largely concerned, the 
leucocytes were found not to exceed 14,000 during an acute febrile 
period." 

lY. Extensive infiltration (" tuberculous pneumonia may cause 
marked increase of white cells, sometimes as great as in croupous 
pneumonia, but this is not invariable. 

Y. Fibroid Phthisis (chronic interstitial pneumonia). — As a rule 
the leucocytes show no increase, but if, as sometimes occurs, we have 
the combination of this condition with cavity formation, the latter 
may increase the count of white cells. 

YI. Fever. — AYhen the temperature is normal, the leucocytes are 
normal, but a febrile state may or may not be accompanied by leu- 
cocytosis (according, presumably, as the fever is or is not due to 
pyogenic organisms). 

YIL Tuhercidin Injections. — At the height of the reaction fever 
the leucocytes almost always rise, the lymphocytes and eosinophiles 
being relatively increased. 

In a general way, the worse the case the higher the leucocyte 
count, yet the signs may be advanced without causing any leuco- 
cytosis if cavities are absent. 

The following tables give some idea of the range of the counts 
in average hospital cases of phthisis : 

Phthisis— Red Cells. 
Between 2,000,000 and 3,000,000 = 1 case. 

3,000,000 " 4,000,000 = 18 cases. 
4,000,000 " 5,000,000 = 25 " 
5,000,000 '■ 6,000,000 = 16 " 



Total 



60 cases. 



PHTHISIS. 



273 



Phthisis — Hemoglobin. 



From 10 to 

" 20 ' 

" 30 " 

" 40 

" 50 " 

" 60 " 

" 70 " 

" 80 " 

" 90 " 



20 per cent = 1 case. 

30 " =0 " 

40 " =4 cases. 

50 " =6 

60 " r= 19 

70 " = 23 

80 " = 16 

90 " =6 

100 " =5 



Total 80 cases. 



Phthisis — White Cells. 
Between 3,000 and 4,000= 5 cases. 



4,000 " 


5,000 = 


4 


5,000 " 


6,000 = 


9 


6,000 " 


7,000 = 


9 


7,000 


8,000 = 


10 


8,000 


9,000 = 


9 


9,000 " 


10,000 = 


14 


10,000 " 


11,000 = 


5 


11,000 " 


12,000 = 


7 


12,000 " 


15,000 = 


25 


15,000 " 


20,000 = 


16 


20,000 " 


30,000 = 


8 


30,000 " 


40,000 = 


3 



Total 124 cases. 

The number of those showing leucocytosis is slightly greater 
than those without it, probably because incipient cases rarely think 
themselves sick enough to come to a hospital. On the other hand, 
some of the cases which appear to have been going on for months 
have normal leucocyte counts. The duration is less important than 
the nature and severity of the process. It is rare to see extensive 
signs in the lungs without leucocytosis — fibroid phthisis excepted. 

QuaUtative Changes in the White Cells. 

1. Many cases show none at all. 

2. When the leucocyte count is normal we may find an increased 
percentage of large and small lymphocytes, such as is commonly 
found in any blood poor in nutritive qualities (see p. 96). 

3. When leucocytosis is present, we usually find the ordinary 

18 



274 



SPECIAL PATHOLOGY OF THE BLOOD. 



marked increase in the percentage of polyniorplionuclear cells at the 
expense of the lymphocytes. 

For example: C. D , male, thirty -two ye'dvs old. Tubercu- 
losis of limgs, with cavities; leucocytes, 17,580. Differential count 
of 1,000 cells shows : 



4. Eosinophiles are increased during the reaction from an injec- 
tion of tuberculin, and also in some cases with cavities in which 
possibly the individual inoculates himself with tuberculin manufac- 
tured in the cavities of his own lungs. 

Otherwise the eosinophiles are increased only at certain physio- 
logical seasons — menses and coitus. In most cases associated with 
leucocytosis they are absent. 

5. Myeloc^-tes were found by Holmes, W. E. May, and myself 
in many cases of advanced phthisis. They averaged .3 per cent. 



Xeusser and his followers have advanced a theory that the oc- 
currence of permuclear basophilia during tuberculosis is a favorable 
sign and marks a system capable of resisting the tuberculous infec- 
tion. The researelies of Futcher and my own attempts to verify 
Xeusser"s theory have not confirmed his findmgs. 

Holmes, of Denver, has studied the leucoc^-tes in phthisis with 
great care and considers that he finds therein means not only of 
diagnosing tuberculosis by the blood alone, but of measuring the 
degree of advancement of the process, and the amount of resisting 
power in the patient. 

I have carefully followed out Holmes" ^^I'ocedures with stains 
seen and approved by him. I can verify most of his statements of 
fact, but some of the inferences which he draws therefrom are, I 
thinlv, wholly unwarranted. The blood changes in pulmonary tu- 
l^erculosis are mainly such as he describes, but they have no diag- 
nostic value, as similar changes are found in a great variety of other 
diseased conditions. The increase of polymorphonuclear forms in 
advanced cases, the increased amount of "debris," the degenerating 



Per cent. 



Polymorphomiclear 

Lympliocyres (small) 

Large lymphocytes dai"ge and transitional) 
Eosinophiles 



83.4 
8.3 
8.4 
0. 



Perin uclear Basoph U ia. 



^ See Appendix. 



BONE TUBERCULOSIS. 



275 



forms, etc., are all characteristic not of tuberculosis alone, but of 
any severe suppurative process. The increase of debris " is prob- 
ably the same datum which Watkins interpreted as an increase in 
blood plates and Goldberger and Weiss as "extracellular glycogen." 
(With Holmes' "undeveloped nuclei " in the leucocytes, compare 
p. 110.) 

II. BONE TUBERCULOSIS. 

Brown' has studied seventy-two cases, Dane' forty-one. Dane's 
study of the blood in forty-one cases of hip disease and Pott's dis- 
ease is a very careful one. Whenever abscesses appeared in con- 
nection with the disease, cultures were taken when the abscess was 
first opened and again later on, and the coincidence of low counts 
with absence of pyogenic cocci and with high counts of secondary pyo- 
genic infection is very notable. Dane's conclusions are as follows. 

1. "High leucocyte counts, especially in hip disease, point to 
the probability that there is, or soon will be, abscess formation; 
but low^ counts do not preclude the presence of abscess, especially 
in long-standing cases. 

2. " If abscess is present, a low count of white cells indicates the 
absence of secondary pyogenic infection (proved by cultures). 

3. " Cases of traumatic origin are generally accompanied by a 
high leucocyte count. 

4. " The leucocyte count bears no direct relation to the temper- 
ature; one case with 30,980 leucocytes (five-year-old girl) showed 
a temperature of only 99.4° at the time of the count. In another 
girl of three years whose temperature ranged between 101° and 
104°, the leucocytes were only 7,224, or subnormal for that age 
{vide infra, p. 445). 

5. " Cases where at the primary operation the pus proved sterile 
show an increase in the leucocyte count when the wound becomes 
infected with pyogenic organisms" (as it always does). 

6. " The red cells are rarely diminished, but the hsemoglobm is 
usually relatively low (mild secondary anaemia in these cases). 
This absence of a diminution in the red cells in these cases is the 
more remarkable because they were almost all in young children 
whose blood is much more sensitive to any deleterious influence than 
that of adults." 

' Transactions of California Medical Society, 1897. 
Boston Medical and Surgical Journal, May 28tli, 1896. 



276 



SPECIAL PATHOLOGY OF THE BLOOD. 



Brown dissents from several of Dane's conclusions. He thinks 
that a case may go on to abscess formation without any increase in 
the leucocyte count. When an increase does take place, he thinks 
it due either to r. secondary infection or to an increased activity of 
the tuberculous process itself without any secondary infection. The 
latter process, however, in Brown's experience causes only a moder- 
ate increase (2,000-3,000), while if a marked increase suddenly or 
gradually occurs he thinks it "most significant of secondary infec- 
tion." With Dane's fifth conclusion he wholly agrees and adds: 
" After the infection (produced by the operation) the leucocytosis is 
very high for a time, and if the sepsis is acute and threatens life, it 
remains high until the crisis is passed." Otherwise it gradually 
falls after the first few days, and if the patient progresses well, it 
disappears. If the pyogenic matter overcomes the recuperative 
power, the leucocytes fall as in peracute pneumonia or peritonitis. 
In such cases the anaemia increases as well. 



(a) As in other forms of tuberculosis there may be none at all. 
(h) The cell changes in purely tuberculous cases is illustrated well 
by Case 17 of Dane's series, a boy of seven whose blood on the day 
of operation for hip disease with large abscess showed 8,932 leuco- 
cytes. The differential count was as follows : 



Eight ounces of pus were evacuated, in which cultures showed the 
absence of pyogenic organisms. 

This case demonstrates that some cases of tuberculous suppu- 
ration have no tendency to produce leucocytosis or to increase in 
the neutrophiles, but influence the blood only by producing what 
might be termed a functional debility of the blood through lack of 
nutritive substances in the plasma. This condition is by no means 
peculiar to tuberculosis, but occurs in a great variety of debilitated 
or cachectic conditions, as already stated. 

(c) But when a septicsemia complicates the tuberculosis, cell 
metamorphosis appears to be accelerated, and we get with the quan- 



Qualitative Changes. 



Per cent. 



Polymorphonuclear neutrophiles 

Small lymphocytes 

Large lymphocytes and transitional forms 
Eosinophiles 



40 
49 
8 
3 



ACUTE MILIARY TUBERCULOSIS. 277 

titative increase of leucocytes such qualitative changes as the fol- 
lowing : 

Per cent. 

Polymorphonuclear neutropliiles 84 

Lymphocytes (small) 9 

Lymphocytes (large and transitional) , 6 

Eosinophiles 1 



This was a case (No. 33 of Dane's series) in which the abscess, 
sterile when first opened, had become inoculated with the staphylo- 
coccus aureus. 

(fZ ) Not every case with leucocytosis shows qualitative changes 
as the above. One of Dane's cases (Ko. 22, a boy of seven) showed 
a leucocytosis of 23,387, but only sixty per cent of these were poly- 
morphonuclear, and two per cent eosinophiles. 

In a case recorded by Dane (No. 32), tuberculous osteomyelitis 
showed 6,083 white cells (subnormal, as the child was only two 
years old) with sixty-four per cent of polymorphonuclear cells. 
The pus from the bone cavity showed no pyogenic organisms on 
culture. Ordinary septic osteomyelitis gives very different results 
(see p. 251). Dane's cases were almost exclusively hip and spinal 
affections. 

The following cases from the Massachusetts General Hospital 
records illustrate tuberculosis of other bones : 



Table XXX. 



Case. 


Diagnosis. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


1 


Tuberculosis of the knee joint 


6,472,000 


9,400 


63 


2 


a u u 


2, 704,000 


8,000 


9 


3 




4,650,000 


6,500 


61 


4 




5,016,000 


5,800 


73 



III. ACUTE MILIARY TUBERCULOSIS. 

Probably there are no important changes in the red cells or hae- 
moglobin. The number of cases on record is too small to enable 
me to speak positively on this point, but the acuteness of the dis- 
ease would lead us to expect the normal or approximately normal 
conditions recorded in the few published cases. 

About the leucocytes we know more. 



278 



SPECIAL PATHOLOGY OF THE BLOOD. 



Quantitative Cha.tges. 

Normal or subnormal counts are the rule. When occasionally 
there occurs a leucocytosis it may be inferred that the miliary proc- 
ess accompanies a suppurative one, and that the latter and not the 
former is responsible for the increased number. 

Warthin' reports a case with autopsy in which he made over 
thirty counts of the white corpuscles, verifying the more remark- 
able results by repetition. Autopsy showed, besides miliary tuber- 
culosis, a cavity in the lower lobe of the right lung and a suppu- 
rating focus about the seminal vesicles containing four ounces of pus 
rich in tubercle bacilli. Whether pyogenic organisms were also 
present is not stated. The leucocyte counts were as follows : 

Table XXXI. 



Day. 


Hour. 


Leuco- 
cytes. 


Remarks. 


December 6th 


10 A.M. 


3,500 






12th 


8 A.M. 


5,000 




u 


18th 


5 P.M. 


3,500 




u 


22d 


10 A.M. 


5,625 




u 


22d 


11:80 A.M. 


4,725 




« 


22d 


3 P.M. 


5,000 




(( 


22d 


5 P.M. 


3,125 




«( 


24th 


8:30 A.M. 


3,750 




«( 


24th 


11 :30 A.M. 


3,750 




u 


24th 


2 P.M. 


2,500 




«( 


24th 


4:30 P.M. 


2,500 




«( 


25th 


8 A.M. 


1,875 


[80 per cent. 


<( 


28th 


5:30 P.M. 


3,750 


Red cells, 4,135,000; haemoglobin. 


(( 


29th 


10 A.M. 


1,250 


(( 


29th 


2 P.M. 


1,250 




a 


29th 


5 :30 P.M. 


3,750 






31st 


12 M. 


1,250 






31st 


6 P.M. 


2,500 




January 2d 


11 A.M. 


1,250 






2d 


5 P.M. 


2,500 






3d 


2 :30 P.M. 


600 


Severe chilL Count repeated several 
times. 


(C 


5th 


8 :30 a.m. 


3,750 




u 


5th 


11 A.M. 


3,137 




u 


5th 


4 P.M. 


8,125 


Moribund, 


u 


6th 


9 A.M. 


10,000 




u 


6th 


10 A.M. 


5,625 




(( 


6th 


11 A.M. 


2,500 






6th 


12 M. 


5,625 




it 


6th 


12:50 P.M. 


Death. 





In another case he found also a subnormal count. Eieder found 



normal counts in two cases. Von Limbeck states that the leuco- 
cytes are normal, but gives no counts. 

' Medical News, 1895. 



ACUTE MILIARY TUBERCULOSIS. 279 

The following cases from the Massachusetts General Hospital 
records illustrate these points : 



Table XXXII. — Acute Miliary Tuberculosis. 



Age. 


Sex. 


Reel cells. 


White 
cells. 


Per cent 
globin. 


Remarks. 




28 


M. 


2,448,000 


550 


35 


]\Iarch 8th. 








1,200 




March 11th. 








1,100 




]March 11th, gave protonuclein gr. xv. 
t.i.d. 












March 13th, differential count: 












Polymorphonuclear, 78 per cent. 












Lymphocj^tes (small), 12 " 












Lymphocytes (large), 9 " 












Eosinophiles, 1 " 








1,300 




March 14th, glands rapidly diminish- 












ing. 












March 18th, died. Autopsy. 






3,296,000 


3,000 


43 


24 






3,300 




First day. 








8,000 




Third day. 








4,400 




Xinth day. 








9,100 




Twelfth day. 


52 


F. 




3,500 


90 


18 


M. 




3,600 




Autopsy. 


40 


M. 




3,750 




Autopsy. 


40 






4,000 






14 


F.' 


3,720,000 


4,400 


45 


Autopsy. 


26 






4,600 




First week. 








3,400 




Sixth week. 


51 


M. 


4,664,000 


4,800 




Autopsy. Chronic phthisis also. 


23 


M. 




4.900 




Autopsy. Differential count normal. 


14 






5,400 


65 


18 


F." 




5,400 


80 


September 21st. 








7,400 




September 24th. No serum reaction. 


29 


M. 




5,600 


64 


Autopsy. Xo serum reaction. 


12 


F. 




6,100 




Autopsy. 


19 


F. 




6,600 




x\utopsy. 


56 






6,800 




First day. 








8,200 




Xiuth day. 








21,000 




Day of death. 


O i 


r . 




1 , ouu 




Autopsy. 


18 






7,600 




First day. 








8,600 




Fourth day. Ninth, death. 


36 


M. 




7,600 




Healed phthisis also. Autopsy. 


20 


F. 




7,800 




:\Iay 14th. 








7.200 




May 22d, death. Autopsy. 


85 




3,920,000 


8,000 


45 


30 




4,500,000 


8,800 


52 




30 


M. 


9,250 




April 18th. 








9,450 




April 20th. Autopsy. 


45 


M. 


5,237,000 


10.000 




xlutopsy. 


38 






12,200 




Autopsy. 


22 


m'. 




12,700 




Phthisis also. Autopsy. 



280 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXXII. — Acute Miliaky Tuberculosis {Continued). 



A Re. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 




78 




2,416,000 


32,000 
/■ 


29 


Diff. coimt 1.000 cells: 

Poly nuclear. 87 per cent. 
Lymphocytes, 11 
Eosinophiles. 0 " 
Myelocytes. 2 " 
Normoblasts = 5. 
Megaloblasts = 2. 

Complicated with diphtheria. 



Case I. of the above table is a striking example of the remark- 
ably low leucocyte cotmt sometimes seen in this disease. The 
cotmts were carefully verified by several competent observers. 



Qual it a five Chau^/es. 

In Warthin's case aboA'e quoted, he repeatedly made differential 
counts of the leucocytes by Ehrlich's methodSj with this average 
result : 



Polymorphonuclear neutrophiles 91.49 per cent. 

Lymphocytes (small) 5.52 " 

Lymphocytes (large and transitional) 3.09 " 

Eosinophiles 0. " 

Myelocytes 2. 



IV. TUBERCULOSIS OF SEROUS ME]\IBRANES. 

1. Tuberculous Peritoxitis. 

The blood condition is exactly as in other forms of tuberculosis, 
except in so far as it is modified by the dram exerted on the blood 
by diarrhoea or by transudation or exudation into the peritoneal 
cavity. Such events concentrate the blood by Avithdrawing water 
and albtimin from it and may give us a normal number of red cells 
per ctibic millimetre, when in reality a considerable anaemia is pres- 
-ent. As a rule, the blood shows a mild secondary ansemia without 
leucocytosis or with leueopenia. This is exemplified in the follow- 
ing table from the Massachtisetts General Hospital records : 



TUBERCULOSIS OF SEROUS MEMBRANES. 



281 



Table XXXIII. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


26 


F. 


3,120,000 


2,240 


58 




28 






2,600 






38 


F.' 


2,900,000 


3,800 


48 




24 


M. 


5,860.000 


3.800 




January 6tli, 1896. 






5,760,000 


5,600 


85 


April 18tli, 1896. 


25 


F. 




8,900 




Tuberculous tube. 


21 


M. 




4,400 






25 






4,700 


52 




27 


M. 




4,900 


64 


March 1st. 








5,500 




Marcli 9tli. 


43 


M. 




5,000 




December 18th, 1895. • 






4,56(),666 


3,250 


76 


January 10th, 1895. 


30 


F. 




5.180 




Tuberculous tube. 


20 


F. 


5,936,000 


5,400 






28 






5,400 






44 


M. 


2,974,000 


5,580 




Pleuritic effusion also. 


24 






5,600 






34 






5,600 






16 


F.' 


8, 840, 666 


6,000 






33 


F. 


4,000,000 


6,000 






37 




6,200 












5,400 






50 


F. 


5,240,000 


6,400 






18 






6,400 


55 




37 


m'. 




6,700 




May 22d, 1896. 


22 




3,552,000 


6,800 


45 


15 




5,112,000 


6,900 


70 


Polynuclear, 44 per cent; lympho- 


19 






7,200 




cytes, 49 per cent; eosinophiles. 












7 per cent. 


16 






7,400 


70 




15 






7,400 






23 






6.800 






33 






7,900 






81 






8,000 






16 






8,700 




First day. 








7,600 




Thirtieth day. 


15 


■ 




9,800 




19 






9,800 






20 






10,800 






47 






11.300 






19 






11,600 


65 




37 






12,400 






19 






14,500 












11,600 






15 






14,600 






16 






16.100 




First day. 








14,200 




Sixth day. 








11,000 




Eighth day. 


6 




4,576,000 


18,000 


52 


Intestines perforated. 






81,900 




Ninth day, after two dry taps. 








18,500 




Thirteenth day, pus and faeces coming 










45 


through tap holes. 








22,900 




Seventy-eighth day. Autopsy. 



282 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXXIII. {Continued). 





Sex. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin . 


£v6rn&<rKS. 








7,000 





May 30th, 1896. 


30 


M. 


5,560,000 


6,800 




44 


F. 




7,000 


73 




26 


M. 


4, 368, 000 


7, 400 


45 




1 T 
1 < 


M. 


A Ck(\A (\(\f\ 


C AAA 
O, UOO 


75 




32 


F. 




8,200 






20 


F. 


4, 200, 000 


8.500 


58 


Tuberculous tube. 


29 


F. 


3,400, 000 


8,600 


30 




50 


F. 


4,600, 000 


10,000 


50 




41 


M. 


5,200, 000 


10,000 






38 


F. 


4.816, 000 


11,200 






21 


F. 


3, 555, 000 


11,500 


65 




27 


F. 




1 6. 900 


76 


Pelvic abscess also. 








18, 300 







I know of no differential counts of leucocytes in tuberculous peri- 
tonitis. Presumably the sluggish metabolism of the cells found in 
other forms of pure tuberculosis exists here and causes an excess of 
the mononuclear elements. 



2. Tuberculous Meningitis. 

Eemarkably few counts are on record so far as I can ascertain. 
Yon Limbeck gives but a single case (with autopsy). Four counts, 
the last on the day of death, showed the following : 



May 22d, 1889: Leucocytes 8,000 

" 23d, 1889: " 8,000 

" 24th, 1889: " 6,000 

" 26th, 1889: " 7,500 

Eieder records two cases, in one of which the leucocytes were 
"normal or subnormal, in the other increased." In both diagnosis 
was confirmed by autopsy. The counts in these cases were as fol- 
lows : 

Case I.— February 26th, 1891 : Leucocytes 7,800 

March 2d, 1891 : Leucocytes 5,900 

Case II.— May 30th, 1891: Leucocytes 14,400 



Tlirck studied three cases, all showing more or less leucocytosis 
(9,600 with 90 per cent polynuclears and no eosinophiles, 17,100 and 
18,100 with 83 per cent polynuclears and no eosinophiles, 20,800 
with 86 per cent polynuclears and no eosinophiles). Blood plates 
and fibrin were not increased. 



TUBERCULOSIS OF SEROUS MEMBRANES. 



283 



Pick ' saw two cases : 

Case L— February 28th, 1890: Leucocytes 6,500 

March 5th, 1890: Leucocytes 8,000 

In the second case there was also no leucocytosis. Autopsy in 
both. Sorensen's' two cases showed respectively 8,300 and 9,400 
leucocytes. My own results in twenty-seven cases are as follows: 



Table XXXI V. — Tuberculous Meningitis. 



Sex. 



Red Cells. 



White 
cells. 



29,900 



Per cent 
lisemo- 
globin. 



Remarks. 



28,000 
34,.S00 



63 



July 8th. 
July 9th. 



Autopsy 



25,900 
23,800 

32,800 
27,800 
23,600 
16,500 
21,000 
19,800 



May 30th. 
June 4th. 

also. 
June 8th. 
June 10th. 
June 12th. 
June 14th. 
June 16th. 
June 18th. 



Tuberculous peritonitis 



M. 



24,800 
32,700 
32,600 



First day. 
Third day. 
Fifth day. Died. 



21,500 



Autopsy. 



20,400 



19,500 



M. 



17,600 



16,400 
29,500 



T. 103^ first day. 
Death, fifth day. 



15,000 



15,400 



55 



14,700 



68 



Pleurisy also. 



M. 



14,400 
19,400 
13,200 , 
19,300 I 



January 25th. 
January 30th. 
February 2d. 
February 6th. Autopsy. 



^ Cited by Rieder. 



284 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXXIV.— Tubeeculous Meningitis {Continued). 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
htemo- 
globin. 


Remarks. 


6 






14,000 
18,' 000 




X Hot \X<X\ . 

Fifth day. 


6 






13,900 
21,400 
17,400 




First day. 

Fourth day, T. 102°. 
Tenth day. 


3 






13,100 






12 






12,000 






8 






11,500 
11,900 




First day. 
Fourth day. 


35 






10,800 






19 






10,000 
11,000 




First day. 
Fourth day. 


10 mos. 






9,200 






22 






8,200 
13,300 




First day. 
Seventh day. 


30 






8,100 






45 


M. 




8,000 






5 






7,500 






40 






7,000 
10,000 




First day. 
Fourth day. 


24 


F. 


4,590,000 


6,600 


86 





In eighteen of my twenty- seven cases there was leucocytosis, 
sometimes very marked. 

It seems therefore that j)nre tuberculous meningitis differs mark- 
edly- from other pure tuberculous processes, in that it has in most 
cases a strong tendency to raise the leucocyte count. Osier's re- 
sults point to the same conclusion.' Ziemke'"^ has recently reported 
a case with 17,500 leucocytes per cubic millimetre. The red cells 
and haemoglobin show, as a rule, but slight changes, as is so often 
found in other forms of tuberculosis. The absence of any increase 

^ " Text-book of Medicine, " 3d edition. 
2Deut. med. Woch., April 8th, 1897. 



TUBERCULOSIS OF SEROUS MEMBRANES. 285 



in fibrin is, Ttirck thinks, of some diagnostic value in excluding 
other types of meningitis. 

* 3. Tuberculous Pericarditis. 

In one case in which tubercle bacilli were repeatedly demon- 
strated in the fluid obtained by tapping the pericardial sac I found 
no leucocytosis. The counts in two others are shown in the accom- 
panying table. I have not met with any other reports on the blood 
in this condition. 



Case. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


1 

2 


19 

48 




4,728,000 


6,200 
7,000 


60 





4. Tuberculous Pleurisy. 

No doubt a large proportion of all pleuritic effusions are tuber- 
culous in origin ; and, so far as I have seen, no high counts are re- 
corded in cases proved by culture or inoculation to be tuberculous. 
The low leucocyte counts in most pleurisies (see above, p. 260) tend 
to show that they are tuberculous and not due to pyogenic organisms. 

Pick mentions that he finds no leucocytosis in tuberculous pleu- 
risy when uncomplicated by phthisis, but reports no actual counts. 

5. Glaxdular Tuberculosis. 

In cases of so-called scrofulous glands, whether in children or 
adults, the blood shows no important changes except that in chil- 
dren the hsemoglobin may be considerably diminished. 



Glandular Tuberculosis. 



No. 


Age. 


Sex. 


White cells. 


Per cent 
haemoglobin. 


1 




20 


F. 


5,600 


75 


2 




28 


M. 


10,900 


65 


3 




7 


F. 


11,000 





Leucocytosis is absent unless an abscess has been opened and 
infected. Whether or not tuberculosis of the abdominal or other 
internal lymph glands affects the blood, I am unable to say. 



286 



SPECIAL PATHOLOGY OF THE BLOOD. 



6. Genito-Ukixary Tuberculosis. 

Here the opportunities for a secondary pyogenic infection are so 
good that in well-marked cases we find the blood of septicaemia 
present. The following cases, all involving the bladder, kidney, 
and the external genitals, illustrate this point : 



Table XXXV. 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 

lltBIllO- 

globin. 




50 






20,100 


58 




23 




* 


15,100 






u 






15.000 


62 


"R in iiTinf^ Tv'iHnoT'' r^Ti^iVu l"^:*/! 
-L . ±J. ILL Ullilc, XVlLlilcX upLlaLctl. 


30 


ii. 


3, 796", 666 


14452 


44 


23 






12.600 




Bladder. 


31 






11,000 


55 


Kidney. 


40 






10,400 






41 


F. 


3,588.000 


10,400 


55 








3,000.000+ 


14.452 






22 


F. 




10.200 






27 






10.100 






56 






10.100 




Testicle and lung. 


32 






9.700 




64 






9.300 






35 


F. 


5,808,000 


8.800 


65 




8 




8,500 


70 




22 


F. 




8,400 






31 


M. 




7.600 


57 




31 


F. 




6.900 


60 




42 


M. 




7.000 




December 18th. 








8.700 




December 26th. 








8.300 




January 11th. 



SYPHILIS. 

Eeiss, in an article in the Archiv f. DennafoJor/ie unci Sijj^hUis, 
1895, Heft 1, says that the general constitutional inlluence of the 
poison of syphilis is best indicated b}^ the condition of the blood. 
In one hundred cases he has arrived at the following conclusions 
regarding the 

Bed Cells and Ho'inorjlohin. 

During the time between the chancre and the secondary symp- 
toms, the red cells are slightly decreased, but this is much more 
marked after the appearance of secondary symptoms and continues 
for a time even after treatment has begun. The haemoglobin sinks 
steadily from the time of the primary lesion on, but is not especially 
affected by the eruption. Even under treatment the haemoglobin 



SYPHILIS. 



287 



never gets quite up to normal and prolonged mercurial treatment 
lowers it, although mercury has at lirst a beneficial effect on the 
haemoglobin as well as on the other constituents of the blood. 

Konried ^ goes further into detail. According to him, in the 
firsfc four to seven weeks after infection, the number of red cells re- 
mains normal, but the hemoglobin begins to fall off, losmg from ten 
to twenty per cent in that time. Afterward it sinks steadily until 
treatment is begun, the number of corpuscles also falling slightly. 

Xewmami and Konried," reporting in 1893 on two hundred cases, 
say that up to the time of the secondary symptoms from twenty -five 
to thirty per cent of haemoglobin is generally lost, without much 
change in the red cells, which sink considerably i]i numljer after the 
outbreak of secondary lesions. Lezius^ likewise finds no diminution 
in the nnmher of red cells until the outbreak of secondary lesions. 

Ewing states : . ''AA'ith the outbreak of secondary symptoms the 
red cells begin to fall rapidly, reaching m untreated cases as low as 
2,000,000 or less (Konried). In ten cases AVilbouchewitch found 
an average decrease of 229,000 cells daily. At the same time the 
haemoglobin continues to diminish and may fall to 5o-2o per cent, 
within a few Aveeks or months." 

All these changes, like those about to be described, are apt to 
be more marked in women than in men. In cases going on to the 
secondary stage untreated, the haemoglobin may sink to as low as 
twenty-five per cent. In the tertiary stages and in hereditary and 
so-called constitutional syphilis " the red corpuscles are much 
more seriously affected, diminishing considerably in number as well 
as in weight and color. The hereditary syphilis of infancy may in- 
deed produce fatal anaemia and very low counts are common, with 
large numbers of nucleated red cells and great deformities in shape 
and size. 

The effect of mercurial treatment on the red cells is interesting. 
Cxaillard ' found that the count of red cells increased during the first 
fourteen days, and the haemoglobin during the first twenty-four 
days of treatment. After that time, if mercury was still given, the 
haemoglobin and later the number of corpuscles began to decline. 

Konried {Joe. cit.) found the haemoglobin to rise during the ad- 
ministration of the first twenty-five to thirty-five inunctions, after 

' International Dermatological Congress, 1892. 
Wiener klin. Woch., 1893, ^'o. 19. 
^Inaug. Dissert., Dorpat, 1889. -^Gaz. des Hop., 1885, Xo. 74 



288 



SPECIAL PATHOLOGY OF THE BLOOD. 



which it began to go down. This was in cases in which treatment 
was begun just after the onset of secondary symptoms. In the 
worst cases it sank even as low as forty-five ]oer cent despite treat- 
ment, and this usually means a bad prognosis and severe tertiary 
symptoms to come. In one of my own cases the haemoglobin was 
only thirty- seven per cent, though the red cells were 4,988,000 
(color index, .37). 

Ewing says : " In one the spleen was much enlarged and con- 
tained gummata, while the blood showed the lesion of grave second- 
ary anaemia, with a tendency toward the microcytic type and a low 
haemoglobin index. In other cases the abundant megalocytes with 
increased haemoglobin closely resembled those of pernicious anae- 
mia." 

Potassic iodide increases the red cells and haemoglobin, but has 
no special effect on the leucocytes. 

Cases often show spontaneous improvement in their anaemia as 
well as in other symptoms. 

Justus' in three hundred cases claims to have observed a peculiar 
reaction of the haemoglobin in syphilis, which does not occur in any 
other disease, and which he considers of much diagnostic value. 

According to him, if in cases in which secondary symptoms have 
not yet appeared, we test the haemoglobin and then give an inunc- 
tion or a subcutaneous injection of mercury, we find that within 
twenty-four hours a very marked fall in haemoglobin has taken place 
(ten to twenty per cent), owing to the action of the mercury on the 
weakened corpuscles. This sudden fall is folloAved by a gradual 
rise until within a few days the coloring matter is at a point 
slightly higher than before the mercury was given. In diseases 
other than syphilis this sudden drop does not occur. After the ad- 
vent of secondary symptoms the peculiar reaction to mercury does 
not occur. My own experience with the test is small. In nine 
cases of active syphilis I found it present. In three inactive cases 
and in thirty-five control cases of various other diseases it was ab- 
sent. In a case of chlorosis the reaction was positive. 

Brown and Dale^ studied thirteen cases of syphilis, and con- 
cluded that the test is unreliable and of little practical value. In 
some of their cases the drop in haemoglobin did not appear until 
several inunctions had been given. 

1 Yerhandl. d. 5 Cong. d. Deut. dermatolog. Gesellscliaft, September, 1895. 

2 Cincinnati Lancet-CKnic, March 24tli, 1900. 



SYPHILIS. 



289 



Jones' examined tliirty-five syphilitics and eighteen control 
cases. Of seventeen cases of active syphilis thirteen gave positive 
results. Jones thinks the test of some value in diagnosis though 
by no means pathognomonic. 

White Cells. 

1. Here the changes are very characteristic. In the first stage 
the leucocytes are either normal or slightly increased, but the per- 
centage of polymorphonuclear forms is almost always notably low, 
and that of the lymphocytes high. If mercury is given at this 
stage, the polymorphonuclear forms begin to increase toward nor- 
mal, and the lymphocytes proportionately to decrease. [Mercury 
given to healthy persons has just the opposite effect, increasing the 
lymphocytes at the expense of the polymorphonuclear forms.] 
Iodide of potassium works exactly like mercury in this respect, in- 
creasing the polymorphonuclear leucocytes in syphilis, while it 
diminishes them in healthy persons. 

2. As the eruption breaks out leucocytosis (12,750 and 16,800 
in two of my cases) generally appears, the proportion of lympho- 
cytes and of eosinophiles usually being increased. Engel describes 
a syphilitic child in whom the percentage of polymorphonuclear 
cells steadily rose as the child got worse. In such cases Engel con- 
siders these cells to be of prognostic importance. P. K. Bro^Ti has 
made a similar observation in bone tuberculosis. Treatment with 
mercury and potassium iodide tends to bring down the count of 
lymphoc;)i;es, while it raises the count of red cells ; and among the 
white cells to increase the polymorphonuclear forms. 

In the tertiarj/ stages, with the severe ansemia which is often 
present, there occur occasionally leucocytosis, not uncommonly with 
small percentages of myelocytes, and a marked lymphoc3rtosis. 
Miiller- has described four cases of anaemia in syphilis so severe as 
to simulate pernicious ansemia very closely. In one the red cells 
sank to 720,000. Laache^ mentions a similar case. 

There are no constant changes in the blood plates. Specific 
gravity follows pretty closely the haemoglobin percentage. 

^Isew York Med. Jour., April 7th, 1900. 

2 Charite-Annalen, vol. xiv. ^ Loc. cit. 

19 



290 



SPECIAL PATHOLOGY OF THE BLOOD. 



Diagnostic Value. 

Justus' reaction of syphilitic blood to mercury, if true, might 
be of great value in distinguishing early syphilis from various other 
causes of debility. 

The occurrence in adults of leucocytosis with increased percen- 
tages of Ijnnphocytes and of eosinophiles, is very suggestive of 
syphilis as against tuberculosis, typhoid, or malignant disease. In 
children, rickets and other diseases may give similar blood changes. 
The chief value of the blood examination, however, in syphilis is 
not for diagnosis but as a measure of the stage and severity of 
the infection. Low hsemoglobin and high percentages of the lym- 
phocytes are characteristic of severe tj^^es. Leucocytosis usually 
means that the case has got beyond the primary stage, while in the 
tertiary stage the presence of myelocytes with a marked anaemia is 
of serious import. 

Certain cases of this last type may closely resemble pernicious 
anaemia, from which, however, they are to be distinguished by their 
low color index, the frequent presence of leucocytosis, and the rela- 
tive infrequency of megaloblasts as compared with the normoblasts, 
in case nucleated red cells are present. 



Table XXXYI. — Syphilis. 



No. 


Age. 


Sex. 


Red cells. 


WMte cells. 


Per cent 

hEemo- 

plobln. 


Remarks. 


1 








24,000 


70 


Meningitis. 


2 


31 






18,600 




Tertiary. Liver? 


3 


27 






16,500 




Hemiplegia. 










12,700 




Eleventh day. 


4 


25 






15,900 


"80 


Cerebral. 


5 


30 






15,000 




T. 100', Avith iritis. 


6 


45 






14.800 




Cerebral. 


7 


40 






13,200 




Cerebral. 


8 


36 






10,350 


65 


Cerebral. 


9 


48 






9.700 




Cerebral. 


10 


53 






9,400 


100 


Cerebral. 


11 


29 




5,880,000 


8.640 


52 


Amyloid liver and spleen. 


12 


33 






8,600 




13 


51 






8.400 


100 


Liver. 


14 


31 






7,200 






15 


49 






6.500 






16 


32 






4,500 




Testicle. 



Dr. Thomas J. Yarrow kindly sends me a blood report of the 
following case, apparently of hereditary syphilis : 



LEPROSY. 



291 





1898. 


Dec. 
20th. 


J dill. 4-111 « 
1899. 




Remarks. 


Red cells 


3.3o0,000 
20,000 










White cells 










Polynuclear. . . . 
Lymphocytes. . . 
Eosinophiles. . . . 


3o.O^ 
4AM 
2(jM 


•26. Tc 
o4.4 ■ 
1-.7 






TLe l iood chang-es here re- 


Normoblasts. . . . 


60 per 
c.mm. 








ansemia and of all symp- 
toms. 



LEPROSY. 

Winiarski (Fetershirrryer medicinische Wochenschrift, 1892, p. 
365) gives a careful study of seventeen cases of leprosy, and P. K. 
Brown^ has watched sixteen cases. They find in young persons 
with mild cases no changes from the normal blood. 

In severe cases, especially in old people, the ans: :::. : oe 
severe (2,290,000 red cells with fifty-four per cent of l-i- i:. i 
and even comparable to pernicious anaemia Tl, 989, 000 red cells 
with sixty-three per cent of haemoglobin In anaemic cases the color 
index is apt to be high, ia one case it was 1.7 (I;. Such severe 
types are associated with an increase of the average diameter of the 
red cells, which explains the high color index. The haemoglobin 
was not relatively low in any case. 

Leucocytes. 

No increase was present in any case. Four cases were subnor- 
mal. The percentage of lymphocytes, as in other debilitated con- 
ditions, is often high fforty-five to forty-seven per cent). 

Bacteriology of the Blood. 

Brown has succeeded in demonstrating the leprosy baciUus in 
the blood of one-half of his cases. Th^ bacilli appear f or tr^e most 
part within the leucocytes, and here tL-y a : : ;la:r iai .r num- 
bers. It is especially in -the tubercular form of the disease that 
Brown has found them. He was unable to cultivate the bacillus. 

Streker'^ has likewise found the bacillus in the blood of four 
cases. 

'San Francisco County Med::-1 S: ir-- July I3th. 1S97. 
^Miinch. med. Woch., 1897. X ;iy. -i'j. 



PART IV. 

DISEASES OF SPECIAL ORGANS. 



CHAPTER VII. 

DISEASES OF THE DIGESTIVE APPARATUS. 

1. Mouth. 

In a case of thrush complicating chronic nephritis the following 
counts were recently recorded at the Massachusetts General Hos- 
pital: October 16th— red cells, 5,000,000; Avhite cells, 16,200; 
hsemoglobin, 52 per cent. October 24th — white cells, 13,800 ; hae- 
moglobin, 55 per cent. 

2. (Esophagus (see Malignant Disease, p. 370). 

3. Stomach. 

The conditions existing in the stomach may influence the blood 
profoundly in three ways : 

(a) They may be such as to prevent the normal absorption of 
nitrogenous material on which the blood, like all tissues, is abso- 
lutely dependent. Then the blood becomes starved. The extreme 
of this condition is the so-called " atrophy of the gastric tubules 
which may produce a fatal ansemia. In lesser degrees the same 
process is at work in many forms of chronic dyspepsia, gastritis, or 
chronic starvation. 

(b) They may lead to severe and repeated hemorrhages. 

(c) They may lead to an auto-intoxication which poisons the 
blood as well as other tissues. 

On the other hand, it is probably through the influence of an 
altered blood serum on the duodenal mucous membranes that ulcer 
of the duodenum is a sequel to severe burns of the surface of the 
body. 

For an account of the influence on the blood of digestion, inges- 
tion of liquid, and starvation, see p. 97. 



GASTRIC ULCER. 



293 



DISEASES OF THE STOMACH. 

ANOREXIA NERVOSA. 

From pure starvation the red cells may get as low as 900,000, as 
in the case mentioned by Martin. In the early stages the blood is 
normal. A recent hospital case showed 8,900 leucocytes with 87 
per cent of haemoglobin. 

GASTRIC CANCER. 
(See Malignant Disease, p. 380.) 

GASTRIC ULCER. 
Red Cells and Hcemoglohin. 

A severe anaemia is common. Out of the 51 cases in Table 
XXXVII., A, 42, 80 per cent, had less than 50 per cent of haemoglo- 
bin, and of the 51 in which the red cells were counted, 17 had un- 
der 3,000,000 red cells per cubic millimetre. The average count of 
red cells at the time when treatment began was 3,372,000. There 
is no single disease, so far as I am aware, in which the red cells are 
so apt to be so low, except pernicious anaemia. Even cancer, as a 
rule, does not fall so low. This is due mostly, I think, to the fre- 
quency of hemorrhage from the ulcer ; it is uncommon to see marked 
anaemia in patients who had never had a hemorrhage. 

This anaemia is all the more striking when we remember that the 
frequent vomiting from which most patients suffer tends to concen- 
trate the blood, increase the number of cells in a drop, and so to 
make the blood seem less anaemic than it really is. This tendency 
to concentration is probably effective in some of the cases observed 
especially by Oppenheimer, ' in which despite great pallor he found 
normal counts of red cells and haemoglobin. 

It is in such cases that the estimation of the dry residue of the blood serum 
would be of real value could it be made short and simple enough for clinical 
work. Grawitz, who is the prophet of this branch of blood examination, 
gives an interesting case illustrating this point. 

A girl of twenty -five, suffering with peptic ulcer, and exceedingly pale, 
showed on counting the corpuscles 4,140,000 per cubic millimetre (no consid- 
erable reduction), and ninety per cent of h.nemoglobin. A second count showed 

^Deut. med. Woch., 1889, No. 42. 



294 



SPECIAL PATHOLOGY OF THE BLOOD. 



4,340,000 corpuscles and ninety-one per cent of liaernoglobin. But the dry 
residue of the serum was reduced to three-fourths its normal amount. The 
serum suffers in anaemia as much as the corpuscles do. Any influence which 
deprived the serum of one-fourth of its normal solids (oedema being absent) 
must have really affected the corpuscles very much. Therefore the corpuscles 
must actually have been reduced to about 3,800,000, the reduction being 
masked by the concentration of the blood from vomiting. Lymph cannot 
have run into the vessels and diluted the serum, for (owing to the vomiting) 
the tide is all the other way. If then the serum is reduced a quarter the cor- 
puscles must be so likewise. Unfortunately, to test the dry residue of the 
blood seium requires more time, skill, and apparatus than clinicians are apt to 
have. It is valuable whenever we wish to know whether or not an anaemia is 
being masked by concentration of the blood. 

In severe cases the usual qualitative evidences of secondary anae- 
mia (deformities, scanty normoblasts) are to be found. 

Table XXXVII., A. — Gastric Ulcer with Hemorrhage. 











White 


"Pot o(^T\f 




No. 


Age. 


Sex. 


Red cells. 


haemo- 


Remarks. 








cells. 


globin. 




1 


QO 

Oiii 




A Q.CKA (\C\C\ 
'I, oD4t,UUU 


90 AAA 


to 


Hemorrhage yesterday. 


2 


20 




3,968,000 


21,100 


45 


Chlorosis. 


3 


52 


F. 


2,031,000 


17,200 


30 


Hem-orrhage and perforation. 


4 


27 




1,860,000 


15,300 


20 


Vomited small amount of blood. 


5 


23 




3,480,000 


15,000 


43 




6 


35 


M. 


1,640,000 


14,900 


18 


Bled four days ago. Diff. count 
500 cells: 
Polynuclear, 74 per cent. 
Lymphocytes, 25 " 
Eosinophiles, .4 " 
Myelocytes, .6 " 
Megaloblasts, 4 
Normoblasts, 1 

Reds stain well. 

Many polychromatophilic. 








2,104,000 


6,100 


24 


Sixth day. Diff. count 500 cells: 
Polynuclear, 60 per cent. 
Lymphocytes, 39 " 
Eosinophiles, 1 " 
Megaloblasts, 0 
Normoblasts, 1 








2,566,006 


7,000 


32 


Thirteenth day. Diff. count 500 












cells: 

Polynuclear, 58 per cent. 
Lymphocytes 39 " 
Eosinophiles, 3 " 
No nucleated reds. 








3,192,000 
4,008,000 




40 


Twenty -first day. 
Thirty-second day. 








6.600 


55 


7 


29 


F. 


1,676,000 


14,750 


36 


Large hemorrhage. 


8 


55 


F. 


3,664,000 


14,800 


45 


9 


22 




4,820,000 


13,800 


50 


Perforation. 



GASTRIC ULCER. 295 



Table XXVII., A. — Gastric Ulcer with Hemorrhage {Continued). 



No. 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hgemo- 
globln. 


Remarks. 


10 


48 




1,448,000 


13,700 


10 


Five days after perforation. Dilf. 














count 500 cells: 














Polynuclear, 86 per cent. 














Lymphocytes, 13.6 " 














Eosinopliiles, .4 " 














Normoblasts, 1 


11 


42 


F. 


2,216,000 


13,500 


32 




12 


32 




3,256,000 


13,000 


35 


November lltli. 








2,564,000 


? 


20 


November 14th. 














Polynuclear, 83.2 per cent. 














S. lymphocytes, 10.4 " 














L. lymphocytes, 3.6 " _ 














Eosinopliiles, 1.8 " 














Myelocytes, i " 














No nucleated reds; general tend- 














ency to small size, very few 














large forms: moderate poiki- 














locytosis. 


13 


24 




5,016,000 


12,000 


52 


14 


29 




3,644,000 


11,400 


35 


Day after hemorrhage of 0 iij. 


15 


72 




3,799,000 


10,700 


35 


Autopsy. 


16 


35 




3,024,000 


10,200 


55 


January 2d. 








3,392,000 


? 


55 


January 13th. 








3,712,000 




45 


February 5th. 


17 


40 




3,868,000 


9,900 


50 


18 


17 




5,000,p00 


9,700 


45 




19 


11 




4,092,000 


9,300 


40 




20 


35 




1,364,000 


17,200 


20 


No autopsy. 








2,224,000 


9,200 


40 


21 


24 


F. 


3,076,000 


8,900 


15 


Bleeding. 


22 


20 




5,374,000 


8,650 


65 


23 


37 




3,267,000 


8,500 


30 


Hemorrhage six days ago. 


24 


45 




3,520,000 


8,400 


35 




25 


37 




4,188,000 


8,100 


35 


Bled one month ago. 


26 


30 


F. 


3,432,000 


7,820 


45 


Hemorrhage pi-evious day. 








4,222,000 


10,600 


75 


Two weeks later. 








4,392,000 


6,700 


70 


Three weeks later. 


27 


44 




4,020,000 


7,600 


33 




28 


29 




5,000,000 


7,400 


50 


Slight hemorrhage. 


29 


26 




1,888,000 


7,400 


19 


Three days after hemorrhage: 














Polynuclear, 57 per cent. 














Lymphocytes, 41 " 














Eosinopliiles, 2 " 














No nucleated reds; reds small but 














not much deformed. 


30 


22 




2,984,000 


7,200 




October 3d. 








3,436,000 


? 


21 


October 20th. 








3,612,000 


? 


34 


November 1st. 


31 


24 


F. 


1,892,000 


7,000 


30 


January 16tli, after hemorrhage. 








2,304,000 


? 


27 


January 22d. 








3,064,000 


3,500 


35 


January 31st. 








3,920,000 


? 


48 


February 10th. 








4,680,000 




55 


February 28th. 


32 


20 




3,340,000 


7,000 


45 



296 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXVII., A.— Gastric Ulcer with H^MonnuAGK (Co?itinued). 



No. 


Age. 


Sex, 


Red ceHs. 


AVhite 
cells. 


Per cent 
hgemo- 
globin. 


Remarks, 


oo 










OK 


r ive days alter hemorrhage. 
Uiii. count oUU cells: 

Polynuclear, 64 per cent. 

Lymphocytes, 35 " 

J2iU!51LH»piHlcIS, JL 














l\OimOUlaSiS, 1. 


34 


33 




4 800 000 


7 000 


40 


35 


26 




3,280,000 


6^800 


30 




36 


24 




4,704,000 


6,500 


45 




37 


30 




2' 544' 000 


6^400 


SO 

Ox) 




oo 


13 




4 4Qfi 000 


fi '^00 


ou 




39 


48 


F. 


4,900,000 


6,200 


40 




40 


23 


F. 


1,672,000 


6,000 


40 


One pint of blood vomited yester- 
day ; blood in stools ; recovery. 


rti 






3 Q20 000 


fi 000 


SO 


jjit^u. beveu Uciys ago. 




24 




lOfi 000 


5,900 


1 '1 




43 


26 


F. 


2 968 000 


5,300 


45 


Exclusive rectal feeding eight 
days. 


44 


19 




4,432,000 


5,000 


58 


Grippe and tonsillitis. 


45 


24 




4 625 000 


5,000 


45 




50 


M 


1 '^54 000 


4 800 


2'Ti 


Polynuclear, 74 per cent. 
Lympliocytes, 23 " 
Eosinophiles, 2 " 
Normoblasts, 2. 


47 


46 


M. 


3,324,000 


4,800 


35 


Fell to 15 per cent after hemor- 












rhage. 


48 


29 




2,584,000 


4,500 


25 


49 


38 




3,616,000 


4,300 


35 


Eleven days after profuse hemor- 
rhage. 


50 


29 


F. 


1,972,000 


4,000 


38 


Recovery. 


51 


26 




4,312.000 


2,000 


45 



Table XXVII., B, — Gastric Ulcer without Hemorrhage. 



Age. 


Sex, 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


17 




5,380,000 


12,100 


60 




22 




5,040,000 


12,000 


45 




21 




5,000,000 


11,800 


70 




39 


F. 


11,100 


68 




24 




6,988,000 


10,700 


48 


Vomiting. 


19 


F. 


5,856,000 


10,650 


90 


40 


F. 


4,400,000 


9,000 


53 




23 


F. 


9,300 


90 




22 


F. 




8,300 


75 




30 


F. 




6,800 


70 




25 


F. 




6,550 


85 




35 


F. 




6,500 


50 


April 27th. 










45 


June 6th. 


47 


F. 




6,300 


57 




38 


F. 




5,800 


60 




19 


F. 




5,600 


68 





GASTRIC ULCER. 297 



Table XXXVII., B. — Gastric Ulcer without Hemorrhage {Cordinued). 



Age. 


Sex, 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


20 


F. 




4,300 


57 




26 




3,216,000 


4,200 


30 




23 




4,680,000 


25 




21 


F. 


5,100,000 




70 





Hcumoglohin. 

As a rule the color index is low. Only one examination in the 
cases of the Massachusetts General Hospital series showed an in- 
• creased amount of haemoglobin per corpuscle, and as this w^as not 
repeated or verified, it may have been a mistake. In most of the 
other examinations the color index was low. 

Yet Osterspey records 1,900,000 red cells with 31 per cent of 
haemoglobin (color index = .81); 3,296,000 with 70 per cent hae- 
moglobin (color index = 1.09) ; 4,048,000 with 84 per cent haemo- 
globin (color index = 1.05). Such cases are certainly rare. 

White Cells. 

Leucocytosis is practically never seen except after hemorrhage 
and during digestion. When patients who have been fed for some 
time by the rectum are first given food by the mouth, the digestion 
leucocytosis may be very great, as in a case of the above series, in 
which the cells increased from 4,000 to 15,5001 The presence of a 
leucocytosis, when the influence of bleeding and digestion is ex- 
cluded, is against the diagnosis of ulcer of the stomach. 



Table XXXYIII. — Duodenal Ulcer. 



No. 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


30 


M. 


3,776,000 


Normal. 


50 




2 


38 


M. 


1,700,000 




17 




3 


53 




1,472,000 


124,000 


20 


September 3d. Diff. count 500 












cells : 














Polynuclear, 75 per cent. 














S. lymphocytes, 22.4 " 














L. lymphocytes, 1.2 " 














Eosmophiles, 1.2 " 














Myelocytes, .2 " 














Normoblasts, 1. 








1,876,000 




19 


September 10th. 








2,148,000 




17 


September 18th. 








2,440,000 




21 


September 24th. 



298 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXXVIII. — Duodenal VijCeh (Continued). 



No. 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 












23 










0 QO/i Ann 


A AAA 




uctODer oLJi. 








0 '7AA nOA 






Anf nVio-r 1 Af li 








0 QOA AAA 




QA 


uciODei ^oa. 












39 


October 30th. 








^ 4.4-0 000 




43 


1> U V t^lliUUl Ubll. 








3,832,000 




45 


November 24tli. 








3,885,000 




48 


December 15th. 


4 


47 


M. 


2,100,000 


12,000 


35 


July 24th, much coffee grounds. 










7,650 




July 29th (five days fasting). 










11,600 




Four hours after meals. 










11,000 




Constant feeding, July 30th. 








2,480,000 


6,000 


38 


August 8th. 








2,630,000 


6,500 


36 


August 21st, operation. 



These figures are given simply to show that the blood in duode- 
nal ulcer undergoes much the same changes as in gastric ulcer, and 
need no further comment. 



ACUTE GASTRITIS AND DYSPEPSIA. 

Acute gastritis or gastro-enteric attacks (Hayem's " e7nhar7'as 
gastrique ") do not affect the red cells or haemoglobin, but are very 
often accompanied by leucocytosis (see Tables XXXIX., A and B). 



Table XXXIX., A. — Acute Gastro-Enteiiitis. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hasmo- 
globin. 


Remarks. 


31 


M. 


7,000,000 


18,000 




Temperature 104°. Well next day. 


8 


F. 


4,800,000 


17,800 


*56" 


Temperature 101°. 


50 


F. 




15,100 


70 


13 


F. 


5, 184,000 


15,000 


85 


Well next day. 


28 


M. 




14,400 




September 17th, temperature 103°. 








12,800 




September 18th, 








9,100 




September 21st, temperature normal 


30 


F. 


4,860.000 


14,200 


"so' 


Well in three days. 


20 


M. 




12,000 


67 


36 


F. 




1 1,600 


68 




23 


F. 


6,244,000 


11,600 


86 


Well in two days. 


17 


F. 


4, 600, 000 


11,000 


70 


29 


F. 




11,000 




Temperature 101°. 


70 


F. 


4,632,000 


10,000 


'96' 




37 


M. 


4,186,000 


9,200 


68 




28 


M. 




6,900 


90 


Temperature 102°. 


23 


F. 


3,860,000 


6,400 


65 




57 


F. 


6,000 




Temperature 101°. 


23 


F. 


5, 144, 000 


5,400 


'95' 




32 


F. 


5,200 


50 


Temperature 100°. 



CHRONIC GASTRITIS. 



299 



Where this is the case, it may help us to exclude typhoid fever, 
which has no leucocytosis. Even a twenty-four hours' dyspeptic 
attack may increase the leucocytes notably, as in Cases 1 and 2 in 
Table XXXIX., A, and the presence of such an increase need not 
make us suspect anything behind the dyspepsia. It is probably to 
be classed as a toxic leucocytosis due to absorption of morbid prod- 
ucts from stomach or intestine. Fibrin may be increased during 
the period of leucocytosis. 

Table XXXIX., B. — Dyspepsia and Gastritis. 



Age. 



Red cells. 



White 
cells. 



Per cent 
hemo- 
globin. 



Remarks. 



24 



27 

26 
23 



37 
30 

41 

49 
18 
60 



M. 



6,280,000 

4,750,000 
4,920,000 
5,016; 000 
3, 678^666 

4,524,000 

4,200,000 
5,016,000 
3,504,000 



22,700 

12,800 
14,000 

11,000 
11,000 
8,924 
7,326 
7,000 



6,000 

4,000 
3,200 
2,800 



74 
55 



77 
75 

68 



45 
50 



Gastralgia ; constipation ; whole 

belly tender. 
Three days later ; well in a week. 
At mealtime, 11,200; four hours 

later, 12,150. 
Dyspepsia. 
Acute gastritis. 

Chronic gastric catarrh. 

Nervous dyspepsia. 

r Before meal, November 1st, 

J 6,000; November 2d, 6,300. 

[ After meal, November 1st, 

t 6,800; November 2d, 7,400. 

Chronic pjastritis. 

Dyspepsia. 

Chronic gastritis. 



CHRONIC GASTRITIS. 
(See Cases 6, 9, and 11, Table XXXIX., B.) 

Here the conditions are different and we never find an increase 
of the white cells, but often a decrease due to malnutrition. Diges- 
tion may produce no leucocytosis, or the increase may be very slight 
and late in appearing (four to five hours after a meal instead of two 
to three hours). It was present m nine out of twelve cases in our 
series. 

Anaemia is very often present and may be extreme. It is be- 
lieved by very high authorities that a lyernicious anaemia may be 
caused by chronic gastritis with atrophy of the gastric tubules. 
The writer has never had the good fortune to see such cases. 

The practical points about the blood of chronic gastritis are : 

(a) The not infrequently severe anaemia. 



300 



SPECIAL PATHOLOGY OF THE BLOOD. 



(b) The not infrequent absence of digestion leucocytosis as in 
gastric cancer, from which therefore the absence of digestion leuco- 
cytosis does not distinguish it. 

The presence of a leucocytosis militates against the diagnosis of 
chronic gastric catarrh, and, if hemorrhage is excluded, points tow- 
ard cancer. 

HYPERACIDITY AND HYPERSECRETIOIsI. 

The leucocytes average higher in these conditions than in chronic 
gastritis or dyspepsia with normal or decreased secretions (see Table 
XL.). Otherwise the blood is not remarkable. 



Table XL. — Hyperacidity and Hypersecretion. 



6 


Age. 




Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 

2 
3 

4 

5 
6 


Adult. 
30 
40 

.40 

28 
57 


M. 
F. 
M. 

M. 

F. 
M. 


5,024,000 
5,768,000 
5,800,000 

3. 340, 000 

4,016,000 
4,160,000 


12,300 
10,800 
10,000 

7,780 

5,994 
3,600 


82 
82 
85 

72 

76 
34 


Chronic gastritis. 

Slight digestion leucocvtosis ; 

12, 270 before meal, 14, 300 three 

hours later. 
Dilated stomach ; no digestion 

leucocytosis. 

Lead poisoning and dilated 
stomach. 


Dilated Stomach. 




Age. 


^ 


Red cells. 


White 
cells. 


Per cent, 
haemo- 
globin. 


Remarks. 


1 

2 
3 


22 
51 
47 


F. 
M. 
M. 


6,216,000 
4,184,000 
4,720,000 
5,000,000 
5,264,000 


10,400 
9,600 
8,000 


83 
55 


Nervous dyspepsia. 
Movable kidney. 


4 
5 


30 
64 


F. 
M. 


6,000 
4,600 


75 
70 



DILATED STOMACH. 

Ill many cases proteid absorption is so faulty that the blood is 
severely starved, but the anaemia may be concealed by the concen- 
tration of the blood brought about by the constant vomiting of large 
amounts of fluid. Kussmaul has shown that patients offoi vomit 
more fluid than they ingest, and it is obvious what must be the drain 
of this process on the fluids of the blood and all other tissues. 



ACUTE ENTERITIS. 



301 



Digestion leucocytosis is often absent, as in cancer or chronic 
gastritis. 

CORROSIVE GASTRITIS. 

The blood was examined in a case of this kind in 1895 at the 
Massachusetts General Hospital with the following result: Ked 
cells, 3,792,000; white cells, 32,500; haemoglobin, lifty-three per 
cent- 

DISEASES OF THE INTESTINE. 

Influence of Saline Cathartics on the Blood. 

Hay' gives the following figures, showing the effect of sulphate 
of sodium in concentrating the blood : Healthy man of thirty-three, 
3:35 P.M. Red corpuscles, 5,025,000; given 85 c.c. of a concen- 
trated solution of sulphate of sodium in water ; thirty-five minutes 
later blood count showed red corpuscles, 6,540,000; sixty-five 
minutes later blood count showed red corpuscles, 6,790,000; four 
hours later blood count showed red corpuscles, 4,930,000. Evi- 
dently much fluid was drawn out of the blood-vessels, and then 
within four hours the tissues had supplied the loss and the blood 
had returned to its normal density. 

Hay also showed that dilute solutions of the same salt had far 
less effect in concentrating the blood. Further he demonstrated 
that if the blood is already concentrated when the saline is given, 
no purgative effect follows. 

Grawitz confirms these results ; he found also that common salt 
still further concentrates the blood (hence its jDroduction of thirst), 
and considers that (as this concentration accelerates coagulation) the 
household use of salt water as a remedy to stop hemorrhage is well 
founded. 

ACUTE ENTERITIS. 

Practically the great majority of cases of acute enteritis are part 
of a gastro-enteric attack, and in Table XXXIX. (see p. 298) the two 
have been lumped together. What was said of that table (p. 299) 
need not be here repeated. Besides the slight leucocytosis there 
mentioned, we may find in cases in which the stools are very wa- 
tery, a temporary concentration of the blood with increased specific 

' Hay : " The Action of Saline Cathartics. " Journal of Anatomy and Phys- 
iology, 1882, p. 430. 



302 



SPECIAL PATHOLOGY OF THE BLOOD. 



gravity and red corpuscles. In infants the lymphocytes are apt to 
be increased at the expense of all the other varieties. Eosinophiles 
may be absent. Thus in a case of subacute colitis following an at- 
tack of influenza pneumonia, Wochnert found ninety-seven ])er cent 
of Ijanphocytes in a total count of 14,000 white cells. The other 
three per cent. Avere polynuclear. ' 



Table XLI. — Enteritis, Colitis, and Dysentery. 



d 


Age. 




Red cells. 


White 
cells. 


Per cent 
haemo- 


Remarks. 


1 


45 


M. 


3,840, 000 


17,000 


50 


Chronic dysentery. August 26th. 










14, 300 




September 3d. 










7,700 




" 5th, dysentery ceased. 










8,800 




20th. 


2 


25 


F. 




17,000 




Chronic entero-colitis. 


3 


Adult. 


M. 


3, 624, 000 


13,000 


58 


Chronic entero-colitis. 


4 


Adult. 


M. 


4,320,000 


12,400 




Ulcerative colitis. 








2,732,000 


10, 600 




Two weeks later. 








4,488,000 


6.000 




Three weeks later; much im- 














proved. 


5 


39 


F. 


6,776,000 


8,900 


100 


Acute febrile dysentery ; bloody 














movements every hour. 


6 


3 


F. 


4,800, 000 


7,900 




Ulcerative colitis. 


7 


Adult. 


M 


4,100,000 


7,560 


72 


Clironic enteritis. 


8 


27 


M. 


4,872,000 


7, 000 




" diarrhoea and tetany. 


9 


20 


M. 


5,008,000 


6.460 


39 


" diarrhoea (tubercular?). 


10 


26 


M. 


4, 900, 000 


5,300 


80 


Bloody stools ten days. 


11 


65 


M 




5.200 


80 


Catarrhal entero-colitis. 


12 


40 


F. 


2,996.000 


5,000 


37 


Chronic colitis. 


13 


27 


F. 


4,500,000 


5,000 


70 


Diarrhoea. 


14 


34 


F. 


3,920,000 


4,200 


71 


Chronic colitis. 



CHRONIC DIARRHCEA. 

(See Table XLI.) 

In acute diarrhoea the other tissues respond to meet the loss of 
fluid sustained by the blood, and the blood is soon normal again. 
But when this process goes on long, the body becomes so wasted 
that the blood must share in the starvation and the albuminoids are 
drained out of it, leaving it watery and poor in corpuscles. A pa- 
tient of Grawitz after years of chronic dysentery had but 1,880,000 
red cells per cubic millimetre, while the serum had twice the nor- 
mal amount of w^ater, and half the normal amount of solids. I 
have seen the count fall as low as 1,928,000 in a case of prolonged 
colitis, with final recovery. In another case the red cells reached 
' Journal of the American Medical Association, February 2d, 1901 . 



CHRONIC DIARRHCEA. 



no lower than 2,440,000, but the haemoglobin was only ten per cent. 
A differential count of this man's blood showed the following: 

Per cent. 

Polymorphonuclear neutropliiles 66.8 

Lymphocytes (small) 24.9 

Lymphocytes (large) 6.0 

Eosinophiles 1.4 

Myelocytes 1.4 

While counting 400 leucocytes I saw 8 normoblasts and 5 me- 
galoblasts. The total leucocyte count was 9,800 per cubic milli- 
metre. 

Cases 1, 3, 4, 12, and 14 of the series in Table XLI. show simi- 
lar conditions. The haemoglobin, however, usually suffers most, and 
the color index is low. 

Leucocytosis is rare, but does occasionally occur, possibly owing 
to some complication or auto-intoxication. 

Table XLII. — Intestinal Obstruction. 



Age. 



Red cells. 



White 
cells. 



Per cent 

haeino- 

globin. 



Remarks. 



1 mo. 



52 
Adult. 



50 
35 

21 

56 

57 
Adult. 

72 

29 

58 
Adult. 



3,120,000 
5,568,000 



F 

M.) 3,504,000 



5,150,000 
4,440,000 
4,272,000 
5,800,000 
4,850,000 

4,480,666 
5,200,000 
5,540,000 



34,200 
22,100 
21,700 
20,800 
18,860 
18,800 
14,666 

12,400 

4,100 

12,200 
12,000 

12,000 
12,000 
11,000 
6,800 
6,000 
6,000 
5,800 
4,000 
4,000 



52 
75 



90 



Intussusception; died. 
Twenty-first day ; hernia. 
Twenty-second day ; autopsy. 
Cancer. 

May 6th; cancer. 

May 17th; cancer. 

No faeces three days. 

No urine two days. 

One day later, no fseces; urine 
drawn by catheter. 

Three days later, bowels moved 
six times. 

Cancer of uterus. 

Chronic obstruction with hemor- 
rhage. 

Obstruction (by a band). 

Cancer. 

Cancer. 



Obstruction by band; operated. 
Cancer. 



Cholera is discussed on p. 226. 
For ap2^endicitis see Abscess, p. 240. 



C04 



SPECIAL PATHOLOGY OF THE BLOOD. 



INTESTINAL OBSTRUCTION. 
Bloodgood's conclusions are as follows: 

In the first forty-eight hours obstruction, if without gangrene or 
peritonitis, gives a leucocyte count of only 6,000 to 16,000. The 
higher the count and the shorter the duration the greater the prob- 
ability of gangrene. If there is a count of over 20,000 within the 
first twenty-four hours, the chances are that gangrene is present. 
After the third day, if the leucocyte count remains high, the prog- 
nosis is good. 

Any pathological condition whatever which produces obstruction 
is followed in a few hours by a rise in the leucocyte count. 

The only point brought out by Table XLII. is that the white 
cells may be increased, especially when the obstruction is cancer- 
ous. Hence the blood count cannot be relied on to help us in the 
diagnosis between obstruction and peritonitis. It is more likely 
that the examination of the amount of fibrin will be useful, as it is 
said to be increased in peritonitis and not in obstruction. 

DISEASES OF THE LIVER. 

CATARRHAL JAUNDICE. 

The serum is colored yellow or greenish-yellow and contains 
bile pigments in solution. It has been asserted that jaundice can 
be recognized here before it shows in the skin or urine. In mild 
cases, i.e., when some bile goes to the intestine and the obstruction 
is not of long standing, the blood is iwactieally normal, as the cases in 
Table XLIII. show. Only one of these cases shows any leucocytosis. 



Table XLIIL— Catarrhal Jaundice. 



Age. 


Sex. 


Red cells. 


white 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


47 






14,700 




Seven weeks. Catarrhal ( ?). 


21 


.M. 




10,500 


"si' 


26 






10,400 


60 




44 


M. 




10,200 






41 






10,000 


62 




25 


F. 


4,310,000 


10,000 


77 










10,000 


90 










8,000 






30 


F. 




9,600 


68 




34 






9.200 







CATARRHAL JAUNDICE. 
Table XLIII. — Catarrhal Jaundice {Continued). 



305 





iOCA. 


ri6Q, CGlIS. 


White 
cells. 


Per cent 
globin. 


IXXjilXOil. AOa 


42 


M. 


2,896,000 




8,775 


47 


Alcoholic gastritis. 


40 






8,200 
8,100 


75 


*46* 






8,000 






28 






8,000 






37 






7,500 






30 






7,500 






26 


M. 




7,500 






21 


M. 


4,800,000 


7,500 


65 




30 


M. 




7,400 


64 




30 


M. 




7,800 






53 


M. 


4,240,000 


6,793 


79 




24 




6,800 






44 






6,200 




Obstruction. 


29 


ii. 




6,200 


'82' 






M. 


4,996,000 


6,000 


78 




24 




6,000 


78 




25 






5.400 


30 


Polynuclear, 78 per cent. 
Lymphocytes, 19 " 






















Eosinophiles, 1 " 












Myelocytes, f " 
























Reds pale, deformed. 












1 normoblast. 


32 




5,600,000 


5,300 
4,700 


75 


March 16th. 


35 


M. 


4,350,000 


4,900 


85 




44 




3,168,000 


4,800 


85 




29 


F. 




4,200 
9,600 


85 




19 


F. 




4,000 







and. the red cells and haemoglobin have not suffered except in the 
alcoholic case in which other causes for ansemia were present. This 
is contrary to the observations of Grawitz, who found, constantly 
leucocytosis, but agrees w^ith those of v. Limbeck and Hayem, who 
never found any increase of leucocytes or any other changes in the 
blood count. Coagulation in this or any other type of obstructive 
jaundice may be very slow, but this is especially apt to be true in 
gall-stone cases even if no jaundice is present. Coagulation may 
be increased to eleven minutes (Osier) and patients may bleed 
to death during operation on gall stones. The amount of fibrin is 
normal. Von Limbeck noticed an increased resistance of the red 
- cells to the influence of distilled water and dilate saline solutions 
which in normal blood dissolve the haemoglobin. He noticed also 
that the size of the red corpuscles was greater than normal, their 
20 



306 



SPECIAL PATHOLOGY OF THE BLOOD. 



volume in a given amount of blood being seventy-seven to eighty- 
one per cent (^.e., they take up seventy-seven to eighty-one per cent 
of the room occupied by the drop), while the normal is about forty- 
four per cent. This was in cases with only from 4,000,000 to 
5,200,000 red cells per cubic millimetre, so that it was evidently 
due not to an overcrowding of the drop with red cells, but to a true 
increase of size in the individual cells. The same fact has been 
attested from a different point of view by the investigations of v. 
Noorden, who found the solid residue increased, and of Hammer- 
schlag ; and Grawitz has noted an increase in the specific gravity of 
the whole blood, though that of the serum remained normal. Nor- 
mal red corpuscles put into the serum of icteric patients increase 
their diameter considerably, so that apparently the serum is respon- 
sible for the change. 

Qualitative Changes. 

Grawitz noted in severe cases that crenation took place much 
more rapidly than usual in freshly drawn blood, and that the rou- 
leaux formation did not take place. This latter point was also 
noticed by Hofmeier' in icterus of the new-born. Silbermann"^ 
noticed in the same disease great deformities in the size and shape 
of the cells. In severe febrile icterus Weintraud noted in the red 
cells the white spots and streaks with active (molecular) movements 
described by Maragliano (see p. 83) as endoglobular degenerative 
changes. 

Summary. 

Normal blood, except for increased size of the red cells and some 
degenerative changes in severe cases. 

Diagnostic Value. 

The constant presence of leucocytosis excludes an uncomplicated 
"catarrhal" jaundice, and points to the probability of malignant 
disease or inflammation (cholangitis, abscess). Syphilis and cir- 
rhosis of the liver might show the same condition of the blood un- 
less the characteristics of syphilitic blood were very marked (see p. 
286). From a severe cholsemia the absence of any marked anaemia 
distinguishes a purely catarrhal case. (For the changes in cholaemia 
see p. 312). 

^ "Die Gelbsuclit der Neugeborenen," Stuttgart, 1882. 
■ 2 "Die Gelbsuclit der Neugeborenen." Arch. f. Kinderheilk., 1887, p. 401. 



CIRRHOSIS OF THE LIVER. 



307 



CIRRHOSIS OF THE LIVER. 
1, Ordinary (Atrophic) Cirrhosis Without Jaundice. 

In the early stages (according to Hayem) neither the red cells 
nor the haemoglobin fall considerably. Most other observers (per- 
haps thinking chiefly of the later stages) report marked anaemia. 
Wlajew^ counted from 3,000,000 to 4,000,000 red cells; v. Lim- 
beck had a case with only 1,500,000. He noted that the count 
might be increased after a tapping in cases with ascites, owing to 
the concentration of the blood from the rapid refilling of the belly 
with serum. Grawitz, on the other hand, noticed precisely the op- 
posite effect in a patient whose blood before tapping had been con- 
centrated by cyanosis, the heart's action being embarrassed by the 
ascites. After tapping, when the heart's action had become easier 
and stronger, the cyanosis disappeared and the blood count fell 
from 4,700,000 to 4,300,000. In v. Limbeck's case it rose from 
4,680,000 to 5,160,000. The moral is that we should draw no in- 
ferences from the count of red cells soon after a tapping. 

The thirty-seven cases in Table XLIV., A., were all advanced and 
their red cells averaged only 3,580,000 -}- per cubic millimetre. 
They steadily decrease as the disease progresses, one case getting 
as low as 1,300,000; but the anaemia may be concealed by cyanosis 
and concentration. 

Qualitative Changes. 
Hayem noticed a curious stickiness of the red corpuscles, a great 
tendency to adhere to each other. Y on Limbeck looked for it, but 
could never find it. Hayem and Maragliano noticed degenerative 
endoglobular changes in the red cells (" etat crihriforme^^). 



Table XLIV., A. — Cirrhotic Liver without Jaundice. 











Per cent 




Age. 


Sex. 


Red cells. 


White cells. 


haemo- 


Remarks. 








globin. 




58 




4,504,000 


29,300 
18,500 


60 


T., 100", Delirium tremens. 
Fourth day. 


35 




908,000 


26,000 


20 


Intestinal hemorrhage. Diff. count 
500 cells: 












Polynuclear, 85 per cent. 
Lymphocytes, 14 " 






















Eoslnophiles, .8 " 












Myelocytes, .2 " 












Normoblasts, 10 












Megaloblasts, 0 






1,732,000 


19,800 


25 


Seventh day. Diff. count 500 cells: 
Polynuclear, 88 per cent. 



^ Ref. in Petersburger med. Woch., 1894, No. 43. 



308 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XLIV., A. — Cirrhotic Liter without Jaundice {Continued). 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
li3?mo- 
globln. 


Remarks. 












Lymphocytes, 10 per cent. 












Eosinophiles, 1 " 












Myelocj'tes, 1 " 












Normoblasts, 2 






2,456,000 


16,900 


23 


Fourteenth day. 






3,098,000 


14,000 


35 


Thirtieth day. 


53 






23,400 




First day. Ursemic symptoms. 








5.800 




Eleventh day. Autopsy. 


51 






18.200 


30 


Haemoptysis. Autopsy. 


53 


F. 


2,950,000 


16.000 




Recent hemorrhage. 


54 






14.000 




Tapped ; 328 ounces. 


63 




3,000.000 


13.000 


55 


With mitral disease. 


41 


M. 


4,300,000 


12,750 


55 


Liver enlarged. Ascites. 


60 






11.800 




47 






11.600 


60 


Autopsy. 


40 




4,896,000 


11.500 


50 


46 






10,500 


60 




63 






10.000 






48 




4,052,000 


9.800 


55 




48 


M. 


4,992.000 


9.000 


62 


Recent hemorrhage. 


53 


M. 


2,120,000 


9.000 


23 


March 15th. 






1,300,000 


7,500 


22 


April 8th. 










15 


April 18th. 










15 


April 29th. 






2.350,000 


6,000 


20 


May 10th. 






2,375,000 


5,300 


26 


May 12th. 






2,450,000 


5,200 


20 


June 10th. 






4,500,000 


7,800 


25 


June 16th. 


50 




3,100,000 


8.400 


45 




50 


M. 


3,440,000 


8,320 


46 


Liver enlarged. 


34 


M. 




7,900 


95 


49 






7,800 




Tapped; 144 ounces. 


38 




5 360,000 


7,600 


55 


56 


M. 




7.500 


68 




57 




3,744,000 


6.400 


58 




43 




2,620,000 


6,200 


35 




53 






6,200 


60 




48 




4,888,000 


6,100 


65 




38 


F. 




5,700 


65 








5,720,000 


5,200 


46 


Differential normal count. 


45 




2,830,000 


5,500 


40 




14 




3,480,000 


5,500 


55 




54 


M. 




5,400 


64 




56 


M. 


4,'680',00b 


5,000 


48 


Liver atrophic, July 12th. 






4.312,000 


4,000 


62 


July 25tli. 


42 


M. 


2,920,000 


4,500 


56 


October 30th. 






13,400 




jSTovember 7th, during digestion. 








15,300 




November 11th, during digestion. 


53 


M. 




3,800 


72 


54 


F. 




3,300 


65 




63 


M. 


3,844,000 


3,000 






50 


M. 


3,568,000 


2,400 


50 




52 


M. 


3,440,000 


2,400 


50 





Thirty-seven cases. 



CIRRHOSIS OF THE LIVER. 



309 



HcBmoglobin . 

Usually the color index is low ; the average was . 66 in the ten 
Massachusetts General Hospital cases. 



White Cells. 

Except after recent hemorrhage none of our cases showed any 
leucocytosis and the average count was 7,240, some cases having 
notably low figures (2,400, 3,000, 4,500). 

Hayem's results agree with this. Yon Limbeck makes no defi- 
nite statement on this point. Kosenstein and Wlajew found leuco- 
cytosis, the latter 12,000 to 17,000. Possibly their cases include 
the forms of cirrhosis luitJi jaundice in which (see Table XLIV., 
B) the white cells are more often increased. 

The forms of hypertrophic cirrhosis ivithoiit jaundice (fatty in- 
filtrated liver) are here classed with the atrophic cases whose blood 
has just been described. 

Table XLIV., B. — CmRHOTic Liver with Jaundice. 



Sex. 



M. 



Red cells. 



3,700,000 
1,024,000 
3,400,000 
3,960,000 



5,016,000 
3,*74(),00() 



2,064,000 
2,904,000 



White cells. 



20,000 
19,600 
19,500 
19.200 
18,200 
15,600 
14,000 
12,400 
12,200 
12,000 
9,300 
8,700 



19,200 

22,000 

4,300 
2,400 



Per cent 
hemo- 
globin. 



30 
36 
50 
47 
65 

65 
65 



50 



50 
54 



Remarks. 



Toxic symptoms. 
Autopsy. 



Delirious. 



Haemoptysis. 
T. 103"-104°. 

Liver enlarged. 
Ascites. 



Delirious. Death. 
Liver enlarged. 



Liver enlarged. 
Ascites. 

Differential count 400 cells: 

Polynuclear, 87 per cent. 

Lymphocytes, 12 " 

Eosinopliiles, 1 

Normoblasts, 1 
Twentieth day. High fever, toxic 

symptoms. 
Twenty-fourth day. High fever, 

toxic symptoms. Autopsy. 
Jaundice only transient. 
Autopsy (hypertrophic cirrhosis). 
Adult cells, 83 per cent. ; young 

cells, 17 per cent. 



Fifteen cases. 



SIO 



SPECIAL PATHOLOGY OF THE BLOOD. 



2. Hypertrophic Cirrhosis with Jaundice. 
Red Cells. 

True (biliary) hypertrophic cirrhosis ivith jaundice has according 
to Hayem an intense anaemia in many cases. In others it has no 
more effect on the blood than ordinary atrophic cirrhosis. The six 
cases in Table XLIV., B, averaged a little lower in the count of 
white cells than the ten atrophic cases, 3,200,000 as contrasted with 
3,580,000. 

Hcemoglohin. 

In a single case of this variety of cirrhosis Hayem found in four 
successive blood examinations a color index of more than 1. His 
counts are as follows : 



Date. 


Red cells. 


White cells. 


Per cent 
hasmoglobin. 


Color index. 


11th 

« 13th 

15th 


1,599,600 
1,884,000 
1,798,000 
1,971,000 


21,803 
18,082 
15,500 


41 

50 
50 
53 


1.27 
1.39 
1.46 
1.40 



Dried specimens showed an increased average diameter of the 
cells as in pernicious anaemia. The patient died January 15th, and 
the autopsy confirmed the diagnosis of hypertrophic cirrhosis. 

The observations of v. Limbeck of the increased volume of the 
red cells in jaundice may perhaps be another example of the condi- 
tion here noted by Hayem. The presence of bile in the blood makes 
all haemoglobin estimations unsatisfactory. 

Only one of our six cases showed this same condition — Case 13 in 
Table XLIV., B. The corpuscles numbered 2,064,000, or forty per 
cent, and the haemoglobin fifty per cent, a color index of 1.25. This 
case was jaundiced at the time of the examination. 

I have seen no confirmation of Hayem' s observations by any other 
writer. 

White Cells. 

Leucocytosis is commoner in this than in the other variety of cir- 
rhosis. Hanot and Mennier found from 9,000 to 21,800 leucocytes 
per cubic millimetre in five cases of hypertrophic cirrhosis, and an 
average of 6,600 in ordinary cirrhosis. Leucocytosis was present 
in four of the six cases of the Massachusetts General Hospital 
series, the average of all six being 9,000. 



PHOSPHORUS POISONING. 



311 



Diagnostic Value. 

The blood of either form of cirrhosis has no diagnostic value, so 
far as I know, except to exclude abscess and hydatids. If no leu- 
cocytosis is present, abscess and hydatid cyst can usually be ex- 
cluded. 

HYDATID CYST OF THE LIVER. 

The only observations which I have met with are those of Hayem 
and Neusser. Hayem states that the blood shows leucocytosis and 
increased fibrin. Neusser considers that the increase of eosino- 
philes, which he finds in hydatids, serves to distinguish them from 
hydronephrosis, dilated gall bladder, etc. 

" Auche in one case ruled out the diagnosis of hypertrophic cir- 
rhosis from the absence of an excess of leucocjrfces." 

In a single case I recorded white cells 34,000. 



EcHmococcus Cyst. 



Age. 


Red cells. 


White cells. 


Per cent hsemoglobin. 


Remarks. 


31 


. 3,664,000 


8,650 


48 


Iceland. 



ACUTE YELLOW ATROPHY OF THE LIVER. 

Grawitz records a case with 5,150,000 red cells and 16,000 white 
cells. 

A single case with autopsy was studied at the Massachusetts 
General Hospital in 1894, the blood showing 5,520,000 red cells, 
12,000 white cells, and sixty per cent of haemoglobin. 

Ewing reports three cases with leucocytosis, 15,000 to 21,000. 
" The absence of rouleaux and early crenation mentioned by Grawitz 
were not noted." 

PHOSPHORUS POISONING. 

Taussig,' V. Jaksch,^ Badt,^ and v. Limbeck* note an increase 
in the normal number of red cells per cubic millimetre. Taussig 
found 8,650,000 per cubic millimetre; Badt, 6,400,000, 6,500,000, 



'Arch. f. experiment. Path, und Pharm., vol. xxx. ^j^jgggj.^^ Berlin, 1891. 
^Deut. med. Woch., 1893, p. 10. - ^ Loc. cit., p. 34. 



312 



SPECIAL PATHOLOGY OF THE BLOOD. 



and 6,800,000 in tliree successive cases; v. Limbeck, 6,500,000 and 
7,900,000. That this increase is not due to concentration of the 
blood through vomiting of liquid is proved by v. Limbeck's last 
case, in which no vomiting whatever took place. 

The count usually falls to normal within a few days. All these 
changes were verified in thirty-three cases at the Stockholm Hospi- 
tal in 1892 (see Stockholm Hospital reports for 1892). 

The white cells in v. Limbeck's second case were increased to 
12,500. In V. Jaksch's five cases the counts were 58,750, 48,000, 
8,000, 4,070, and 3,400. 

CHOL^MIA. 

When jaundice is intense and long standing, as in complete ob- 
struction of the bile ducts by gall stones or tumors, the blood is 
weakened very notably, and haemoglobin and the count of corpus- 
cles fall steadily. Very little is to be learned upon the subject from 
the literature, but the qualitative changes mentioned under catarrhal 
jaundice are much more marked, and leucocytosis is apt to be pres- 
ent. I have studied the blood in a case of fatal chronic jaundice 
without fever and for which at autopsy no cause was found. The 
leucocytes ranged between 12,000 and 14,000. 

GALL STONES. 

Netter' and Sittmann^ have found pyogenic organisms in cultures 
from the blood of patients with gall stones, as have also Gilbert 
and Girode.^ The slow coagulation is of great surgical importance. 

" The pneumococcus of Frankel and streptococcus pyogenes were 
obtained from the blood in one case each, both complicated by 
hepatic abscess, by Canon and by Zaucarol." 

Of the 22 cases of this disease examined at the Massachusetts 
General Hospital 2 were complicated with cholangitis (see Table 
XLV., A). Excluding these 2, leucocytosis was present in only 
4 of 20 cases. The red cells were low in 2 cases (2,800,000 and 
3,900,000). 

The absence of leucocytosis helps us to distinguish the disease 
from peritonitis and appendicitis, and excludes suppurative cholan- 
gitis. 

' Progres Medical, 1886, No. 46. 

2Deut. Arch. f. klin. Med., 1894, p. 823. 

2 La Semaine Med., 1890, No. 58. 



GALL STONES. 
Table XLV., A. — Gall Stones. 



313 



ge. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hsemo- 
globin. 


Remarks. 


25 






28,200 






39 


f'. 


4,768,000 


24,000 




Cholangitis also. 


30 


F. 


4,820,000 


20,000 




Cholangitis. Autopsy. 


68 


F. 


4,610,000 


18,800 






29 


M. 




16,200 




December 16th. 








13,200 




December 18th. 








10,000 




December 21st. 


60 






14,800 




First day. Pus in gall bladder. 








20,700 




Fourth day. 








15,000 




Fifth day. Operation. 


40 


F. 


4,520,000 


18,000 




60 


F. 


12,500 


72 


Temp. 100.5°. 








11,500 


70 


25 






11,600 






46 




4,176,000 


11,400 


45 




63 






11,300 




Obstructive jaundice. 


39 




4,168,000 


10,500 


65 


No pain. 


37 






10,300 




In colic. 


40 


M. 




10,250 






60 




4,386,000 


10,200 


45 




55 




10,200 




In pain. 






4,448,000 


10,000 


58 


Sixth day. Operation. 


49 


F. 




10,000 


90 


Jaundice. 


40 






9,900 






47 






9,800 


85 




56 






9,700 






41 






9,400 


90 


No pain. 


32 






9,400 




No pain for two days. T. 100°. 


38 






9,400 




Colic. 








5,200 




Colic. 


82 






9,200 




No colic. 


45 


f". 




9,200 


100 




88 


F. 




8,900 


60 


Distended gall bladder. 


25 


F. 


5,072,000 


8,800 




Jaundice. 


40 






8,800 




No pain. 


46 






8,200 




Colic. 


27 






8,200 




Day after colic. 


22 


M. 


3,288,000 


8,000 




Jaundice. 


25 


F. 


4,900,000 


8,000 






54 




7,800 




Between attacks. 


50 






7,700 




Deep jaundice. 


87 






7,600 


60 


54 


F*. 




7,600 


80 




40 






7,400 


60 


August 25th. 








8,700 




August 27th. 






4,336,000 


11,500 


50 


August 81st. 








15,100 




September 6th. 






8,636,000 


10,600 


40 


September 7th. 


48 






7,400 




29 


f'. 


2,844,000 


7,400 






57 


F. 


7,400 


85 




37 


F. 




7,800 




October 1st. 








8.200 




October 5th. 


48 






6,700 




Between attacks. 



314 SPECIAL PATHOLOGY OF THE BLOOD. 



Table XLV., A. — Gall Stones {Continued). 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


58 


M. 




6,000 


64 




57 


F. 




5,400 


68 




51 


F. 




5,300 


63 




28 






5,200 




In colic, proved at operation. 


24 


M. 


4,320,000 


4,000 




Recurrent pain and jaundice. 



CHOLANGITIS. 

Here the leucocytosis is well marked whenever the inflammation 
has got beyond the catarrhal stage (see Table XLV., B), and helps 
us to exclude simple impacted gall stone, with or without colic. Can- 
cer may or may not produce leucocytosis, but does not usually in- 
crease the fibrin network ; it is said by Hayem that cholangitis does 
increase it. 



Table XLA"., B. — Cholangitis. 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Remarks. 


1 




F. 


4,800,000 


50,000 


Suppurative cholangitis. 


2 




F. 


6,400,000 


30,000 


3 




F. 


4, 960,000 


22.000 




4 


"21" 


M. 


4,976,000 


14,800 


Jaundice and cbolaemia. 


5 


65 


M. 


14. 186 


Gall-stones; chills. 


6 








11,000 


October 20th. Operation October 22d. 








Abscess of liver. 


7 


28 


M. 


6,640,000 


9,000 


Catarrhal. 








5,592,000 


6,800 




8 


34 


F. 


4, 770, 000 


4,400 


Catarrhal. 



Table XLV., C. — Cholecystitis. 



Age. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


48 




23,000 




First day. Infectious. 






15.500 




Third day. 


36 




22,600 


60 


Suppurative. 


32 




15,600 


73 


Gall stones. 


25 




12,200 


60 




58 




10,700 


80 




50 




8,300 










46,300 




Ten days later. Suppurative. 


44 


3,602,000 


6,600 


50 


Typhoid. 



HEMORRHAGIC PANCREATITIS. 



315 



The blood does not differ from that of cholangitis with suppu- 
ration. From cancer it may often be distinguished by the absence 
of increased fibrin network in cancer, while it is always increased 
in suppurations. 

ABSCESS OF THE LIVER. 
In all but one of the cases seen by the writer (see Table XL VI.) 
the leucocytosis has been very marked. I have never been able to 
account for its absence in that case. 



Table XL VI. — Abscess of the Liver. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


20 


M. 


4,533,000 


33,200 




January 11th. 








48,000 




January 14th. Operation. 


15 


F. 


3,750,000 


26, 800 




Operation. 


60 


F. 


4,460,000 


18,000 




Operation. 


28 


M. 




12,600 




33 


F. 




11,000 




November 3d, 








17,500 




November 4th, 11 a.m. 








19,200 




November 4tb, 2 p.m. 








20, 600 




November 5th, 10 a.m. Operation ; 












autopsy. 


26 


M. 


2,664,000 


10,200 


33 


October 19th. 






12, 000 




October 20th. 








15,000 




October 21st. October 25th, au- 






3,440,000 






topsy ; streptococci. 


51 


F. 


9,600 







CANCER OF THE LIVER. 
(See Malignant Disease, p. 385.) 



GUMMA OF THE LIVER. 

Von Jaksch in a single case found red cells, 2,756,000; white 
cells, 6,100. 

DISEASES OF THE PANCREAS. 

HEMORRHAGIC PANCREATITIS. 

Opie records a leucocytosis of 19,600 in a case operated by 
Bloodgood (Johns Ho^jMns Bulletin, January, 1901). 

At the Massachusetts General Hospital we have had a case 
in which the following are recorded : — 22,800, 9,200, counts of white 
cells. 



316 SPECIAL PATHOLOGY OF THE BLOOD. 



Acute Hemorrhagic Pancreatitis. 



Age. 


White cells. 


Per cent haemoglobin. 




26 


11,200 
23,000 
24,000 






50 


100 






Fourth day. 



DISEASES AFFECTING THE HEART. 

PERICARDITIS. 
(See Inflammation of Serous Membranes, p. 265.) 

ENDOCARDITIS. 
In many cases of acute endocarditis the blood shows no changes. 
In others, whatever alterations there may be are covered up by those 
involved in the rheumatic arthritis associated with the endocarditis. 

ULCERATIVE ENDOCARDITIS. 

In ulcerative or malignant endocarditis^ we may find the signs of 
a pyogenic infection (see p. 231). Sometimes pyogenic cocci can be 
cultivated from the blood, and if present may he of the greatest value 
in a diagnosis always difficult to make. 

Grawitz goes so far as to say that in doubtful cases repeated 
negative results of cultures from the blood make it unlikely that 
ulcerative endocarditis is present. 

Sittmann' considers that important help may be given as to the 
position of the primary focus of infection by the nature of the or- 
ganism present in blood cultures — i.e., the pneumococcus pointing 
to the lung, the colon bacillus to the intestine, etc. 

Red Cells. 

As in all forms of septicaemia marked anaemia rapidly develops, 
more rapidly probably than in any other disease. The haemoglobin 
loses about equally with the corpuscles, according to most observers 
■ — that is, the blood destruction is so rapid that the red cells do not 
get thin before they die, as is usually the case, but are cut off in the 
prime of health. 

Further evidence of rapid blood destruction is seen in the 
haemoglobinaemia often present. 

Roscher {loc. cit.) records counts of 4,400,000 and 2,750,000, 
both fatal cases. In one case seen by the w^riter the count was 
3,792,000 with fifty-eight per cent, of haemoglobin. 

^ Loc. cit. 



ULCERATIVE ENDOCARDITIS. 



317 



Temperature. 


White cells. 


105= 


17,000 


99° 


13,700 


103° 


15,500 


101.5° 


18,000 


101.5° 


21,300 


101° 


18,800 


104.5° 


13,000 



JVhite Corpuscles. 
Eieder reports a single case showing these variations 

January 2d, 1891 

" ' 3d, 1891 

8tb, 1891 

lOth, 1891 

12tli, 1891 

18th, 1891 

22d, 1891 

February lltli, the patient died. 

Pee found leucocytosis. Eoscher in two cases found: Case I. : 
8,800 leucocytes; the patient died in two days. Case II. : 16,800 
and 12,000. Krebs in one case found: October 27th, 15,500; 
October 28th, 44,200; the patient died the same day. 

"Grawitz reported 168,000 leucocytes in one case." 

Twenty-two cases were counted at the Massachusetts General 
Hospital with the following results : 

Table XLYII. — Ulcerative Endocarditis. 



Age. 



Sex. 



Red cells. 



White 
cells. 



Per cent 
hsemo- 
globln. 



Remarks. 



21 



8 yrs. 
11 mos. 



4,216,000 



29 
18 

27 
29 
35 



34,300 
39,200 
27,000 
47,600 

30,100 
15,800 
18,100 
26,100 
27,000 
27,500 
27,400 
25,000 
16,600 
25,700 
27,840 
18,100 
22,000 
22,800 
22,700 
20,400 
20,300 
19,100 
18,900 
31,300 

20,400 



50 



75 



twenty- 



1 Aortic stenosis. 
Mitral insuf- 
ficiency. 



Third day. 
Tenth day. 

Seventeenth day. Died 

first. No autopsy. 
May 27th. 
May 30th. 
.hme 17th. 
November 20th. ^ 
November 23d. 
November 27th. 
December 3d. 
December 9th. 
December 22d. 
May 22d . 
May 24th. 
May 26th. 
May 28th. 



Autopsy. 

(Six months' fever.) 
Autopsy. 

Pneumonia, January 28th, 1899. 
February 4th, 1900. No signs but 

a systolic murmur and chills. 
February 11th. 



318 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XLVII. — Ulcerative Endocarditis {Continued). 



Age. 



Sex. 



35 



3 yrs. 
11 mos. 
44 



21 



28 
32 
23 



Red cells. 



2,718,000 
8,996,000 

5,330,000 

3,792,000 
3,*884,bbo 

4,272,000 
8,560,000 



2,852,000 
3,652,000 



White 
cells. 



20,900 
40,400 
31,000 
37,400 
63,700 
37,150 



18,800 
8,600 

18,300 

29,200 
35,800 

15,200 



13,500 

18,400 
18,000 
12.600 
14.500 
20,400 
24,000 
11,300 
9,000 
11,700 
18,700 
13,900 
10.000 
8,900 
7,900 
7,600 
5,200 



11,900 

10,100 
8,800 

2l",86o 
15,100 
6,200 
9,800 
3,000 



Per cent 
haemo- 
globin. 



55 



45 

42 
50 
48 
58 
55 



45 



50 



45 



35 
50 



Remarks. 



February 15tli. 
February 21st. 
February 23d. 
February 25th, 
March 1st. 
March 4th. 

March 7th. Autopsy. Malignant 

endocarditis. 
April 7th. T. 102°. Pneumonia. 
April 10th. Pneumonia gone. T. 

99°. 

April 14th, 8 A.M. T. 104.5°. Aor- 
tic and mitral. 

6 P.M. 

April 15th, 7 a.m. Culture of 

blood (14th) . Pneumococci. 
Polynuclear, 86 per cent. 
Lymphocytes, 14 *' 
Eosinophiles, 0 " 
No autopsy. 

October 18th. 
October 22d. 
Januar)^ 18th. 
January 14th. 
January 16th. 
January 18th; died. 
January 8th. 

Pulmonary embolism. 
March 15th. 

April 6th. No autopsy. 

Autopsy. 

Hyperplastic. 

Autopsy. 

December 15th. 

Polynuclear, 91.2 per cent. 

Lymphocytes, 6.7 " 

Eosinophiles, 2.1 " 

December 27th. 

December 31st. 

January 7tli. 

January 14th. 

Januar}' 15th. 

January 26th. 

January 80th. 

February 24th. 

March 8th. No autopsy. 

Polynuclear, 77.0 per cent. 

Lymphocytes, 22.5 ." 

Eosinophiles, .5 " 

No nucleated reds. Autopsy. 



ULCERATIVE ENDOCARDITIS. 



319 



Practically the same are the counts in the following cases of 
apparently " benign " endocarditis with fever and rapidly shifting 
murmurs, the seventh complicating chorea in a boy of thirteen. 



Table XL VIII. — "Benign" Endocarditis. 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
hasmoglobin. 


Remarks. 


56 


F. 




50,100 




November 24th. 








35,800 




November 27th. 








36,600 




November 30th. 








22,800 




December 7th. 


4 






29,600 




Twenty-first. T. 102°. 








28,500 




Twenty-second. T. 98°. 








19,600 




Twenty-fifth. 


28 






24,800 




Twenty-fourth. 








11,700 




Twenty-fifth. 


11 




4,728,000 


24,500 


55 


First day. 






17,700 




Seventh day. 








14,000 


55 


Fourteenth day. 








15,100 










10,800 


55 










10,100 


34 




37 






24,000 


80 


First day. 








16,000 




Fourth day. 








13,600 




Fifth day. 


29 






21,320 




Pregnancy four months. 


13 


M. 




20,600 




May 26th. T. 102^-104°. 








17,900 




May 29th. 








18,700 




May 31st. 








16,800 




June 3d. 








21,200 




June 4th. 








27,400 




June 8th, 








22,700 




June 11th. 








24,200 




June 13th. 








21,900 




June 15th. 








26,100 




June 17th. 








26,800 




June 19th. 








17,400 




June 23d. 








28,700 




June 26th. 








21,200 




July 2d (outdoors). 








21,300 




July 4th. Left the hospital July 












19th. 


17 






19,800 




December 16th. Mitral insutfi- 












ciency. Renal colic. 








19,200 




December 20th. 


26 






12,000 




Salpingitis. 



Diagnostic Value. 

(a) Blood cultures should never be omitted in cases of suspected 
malignant endocarditis. When positive they are of great value. 
(b) In excluding typhoid, malaria, and miliary tubercle the presence 
of leucocytosis is important. I saw within a few months a case in 



320 



SPECIAL PATHOLOGY OF THE BLOOD. 



whicli several consultants had made the diagnosis of typhoid, but in 
which the presence of marked and persistent leucocytosis and the 
absence of a typhoid serum reaction convinced me that the case was 
one of ulcerative endocarditis. This has since been verified. 

MYOCARDITIS. 

Whenever stasis and disturbance of the circulation result from 
weakness of the heart wall, blood changes identical with those 
described under Valvular Heart Disease are present. Otherwise the 
blood is normal. 

Table XLIX. — Myocarditis. 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


51 






30,000 


75 


JSTo autopsy. 


54 






13,200 


68 


Mitral disease with broken com- 












pensation. 


62 






12,900 






53 




4,944,000 


11,800 


45 


Broken compensation. Chronic 












bronchitis. 


60 






10,700 






63 






10,700 




Mitral insuflSciency. 


75 






8,800 




Syncope. Chronic interstitial 












nephritis. 


58 






8.300 


63 


Progressive muscular atrophy. 












Arthritis deformans. 


55 






7,400 






68 






7,200 




Chronic interstitial. 


67 






6,700 




Chronic interstitial. 



VALVULAR HEART DISEASE. 

Grawitz divides valvular heart disease into three stages with 
■corresponding blood conditions : 

1. Stage of full compensation : blood normal. 

2. Stage of acute failure of compensation : blood diluted (Oer- 
tel's "plethora serosa"). 

3. Stage of chronic stasis and cyanosis : blood concentrated for 
the most part; at times diluted as well. 

1. A valvular lesion j^er se has no effect on the blood. 

2. When compensation fails and blood pressure is lowered, we 
find {especicdlym the venoushlood) that the fluid from the surround- 
ing lymph spaces has made its way into the vessels and diluted the 
blood. The specific gravity falls, red cells and hsemoglobin are 
lower than before, while the white cells are unaltered, and the plas- 
ma is shown to be more watery than before, as well as of increased 



VALVULAR HEART DISEASE. 



321 



quantity per cubic millimetre. All these changes are less marked 
in capillary blood, and hence are rarely observed. 

3. If the heart adjust itself partially to the increased work it 
has to do, and to the chronic passive congestion of the internal 
organs and at the periphery, the blood is concentrated, probably in 
part by transudations into serous cavities and lymph spaces, and in 
part by the increased excretion of moisture by the lungs. The 
specific gravity and the number of red cells are increased, especially 
in the capillaries, and to a less extent in the venous blood (the con- 
ditions being just the reverse of those in acute heart failure, stage 
^o. 2) . This is the condition usually found in heart disease with 
chronic venous stasis (passive congestion). 

But this concentrated condition of the blood may be offset from 
time to time by fresh weakening of the heart and lessening of blood 
pressure, and the combination of the two conditions may result in a 
normal blood count. 

The condition of concentrated peripheral blood with the count 
of red cells above normal is that most commonly seen in chronic 
heart disease with stasis. 

Von Limbeck finds that aortic lesions are more apt to show a 
normal or diminished blood count, while mitral disease is more apt 
to be accompanied by the temporary dilutions and long-standing 
concentration above described. He does not explain the cause of 
this, and it does not coincide with my cases. One of his patients 
with double mitral lesion showed a decrease of 1,170,000 red cells 
(from 7,500,000 to 6,330,000) after exertion. When the patient 
was quiet, the lesion was compensated ; on exertion compensation 
temporarily failed, blood pressure was lowered, and the blood di- 
luted. 

Sadler^ found considerable anaemia in three out of four cases of 
aortic disease, while only two of seven patients with mitral lesions 
showed anaemia. 

Schneider's^ results were similar in that he found the red cells 
normal in the aortic cases and increased in the mitral ones. 

Hayem found anaemia most common in aortic regurgitation, 
especially in young people. 

In the Massachusetts General Hospital records there have been 

a strikingly large number of cases of mitral disease associated with 

severe anaemia (see cases 2, 10, 14, and 88 of Table L.). The counts 

^Loc. cit., p. 33. ^ijiaug. Dissert., Berlin, 1888. 

21 



322 



SPECIAL PATHOLOGY OF THE BLOOD. 



of red cells in twenty cases average 3,400,000, and nucleated red cells 
were found in three cases. These were all of them supiwsed to be 
chronic cases without any active endocarditis, septic or benign, and 
were for the most part afebrile. In view of the marked anaemia 
and leucocytosis, however, I am in doubt whether the endocarditis 
was really as dormant as the temperature and the absence of chills 
or embolism would suggest. 

In the cases of aortic disease due to arterio-sclerosis, there was 
no considerable ansemia or leucocytosis. 

White Corijuscles. 

Almost all writers whom I have consulted agree that the leuco- 
cytes are normal unless some complication occurs. Yet in a large 
number of the Massachusetts General Hospital cases the leucocytes 
were steadily increased, while the red cells were diminished (see 
Table L.) This leucocytosis cannot be explained as the result of 
stasis, since it is rare in aortic disease or in myocarditis, despite 
stasis, and is found chiefly m mitral cases. That stasis plays a 
part in the blood counts of congenital heart disease seems evident 
from the cases next to be mentioned, in which the red cells are in- 
creased only about forty per cent., while the white are often one 
hundred per cent, more numerous than normal. 

The apparently normal count of red cells in some of our cases 
may have been due to the covering up of an ansemic or diluted con- 
dition of the blood by concentration, the resultant of the two forces 
being an apparently normal count. 

In the 91 cases of mitral disease tabulated on pages 323-325, 
there aire 51, or 56 per cent, showing leucocytosis of more than 
11,000, and 32 with over 16,000 leucocytosis. In some of the cases 
there was pulmonary infarction or nephritis as a complication, and 
these lesions may have influenced the count. 

The polynuclear cells are proportionately increased. In expla- 
nation of the ansemia and leucocytosis of mitral disease and the 
lack of these phenomena in aortic disease, I conjecture that mitral 
disease is rarely long dormant, and that the " failures of compensa- 
tion," for which my cases sought the hospital, were associated with 
or due to fresh vegetative or thrombotic processes on the valves. 

(Edema and diuresis have in themselves little or no constant 
effect upon the blood, as a recent observation of Petrowsky's has 
demonstrated. 



CONGENITAL HEART DISEASE. 



m 



CONGENITAL HEART DISEASE. 

In the cyanosis accompanying this affection very high blood 
counts are reported. Gibson found : 



Case. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


1 


8,470,000 
6,700,000 


12,000 
12,000 


110 
92 


3 





Carmichael reports, red cells, 8,100,000, white cells, 16,000, in 
a single case, and Toeniessen counted 8,820,000 and 7,540,000 in 
two similar cases. In one case entirely without evidence of any 
stasis I counted 8,431,000 red cells per cubic millimetre. Town- 
send has collected 30 such cases with counts ranging from 6,000,000 
to 9,000,000. How such cases are to be explained I do not know; 
the ordinary explanation of concentration of the blood will not hold 
in cases in which no stasis or lack of compensation exists, yet the 
skin is blue and the blood counts are enormous. 

There is no doubt that the peripheral capillaries always contain 
more corpuscles per cubic millimetre than do the veins. Numerous 
reports from various observers agree upon this. Whether this is on 
account of the loss of water by perspiration and consequent drain 
of blood from the skin capillaries is uncertain, but in congenital 
heart disease both capillary and venous blood is overcrowded with 
corpuscles and the explanation is difficult. Hayem in a case of 
this sort reports 7,000,000 red cells with a decrease in the average 
diameter. 



Table L.— Mitral Valve Disease and Its Complications. 













d 


Lesions. 
















S o 
















Red cells 


White 
cells. 


Per ct 
[emogl 






r ft 


Remarks. 


6 




X 

03 






Mitral. 


Aortic. 




•z 


< 












o 




1 


26 






44,000 


70 


M. 






Died same day. 


2 


39 




3,448,666 


43,150 


55 


M. 


A. 




July 5th. Polynuclear, 71.4 ; lympho- 




















cytes, 27 ; myelocytes, 6 ; masts, 4. 
July 9th. July 10th, autopsy. Fresh 
and old endocarditis. 








3,596,000 


8,800 


43 








3 


30 






32,000 


62 


M. 


















Ruptured 
comp. 








4 


44 




4,480,666 


20,400 
27,000 


40 


M. 






Temp., 100°. 

Fifth day. Purpuric spots. 



324 SPECIAL PATHOLOGY OF THE BLOOD. 



Table L. — Mitral Valve Disease and Its Complications {Continued). 



6 


• 

< 


X 


Red cells 


White 
cells. 


Per cent 
haemoglobin. 


LES 

Mitral. 


>IONS. 

A ortic. 


Tri- 
cuspid. 


Remarks. 


— 
5 


32 


~ — 





30,000 




M. 
















19,000 










First day with infarcts. Temp., 102°. 


6 


31 






23,000 


78 


M. 




T. 


Third day. Died on fifth. 


* 


36 






22,600 




M. 


A. 




No fever. 














Double. 
















22,600 










Fourth day. 










24,600 










Sixth day. 










19,000 










Seventeenth day. 


8 


23 






22,400 




M. 




T. 


Pulmonary infarction. 


9 


8 






22,100 




M. 








10 


8 




^,d^j4,U00 


22,tKX) 


35 


M, 






• 

With nephritis. Polynuclear, 88 ; lym- 




















phocytes, 12 ; eosinophiles, 0 ; 2 




















normoblasts. (Count 500.) Died. 


11 


19 






20,800 


65 


M. 
















Stenosis. 
















11,700 










Four days later. Temp., 96°. 


12 


25 




3,756,000 


20,700 


35 


M. 


A. 




April 10th. 












Double. 










3,680,000 


13,000 


35 








April 20th. Temp., 104.6°. (Count 500.) 




















Polynuclear, 86.6 per cent.; small 




















lymphocytes, 8.6 ; large lymphocytes, 




















4.4 ; eosinophiles, .2 ; myelocytes, .2 ; 




















1 normoblast. No autopsy. 


13 


50 






20,500 




M. 






Dilated and hypertrophied with pul- 




















monary infarct. 


14 


16 


F. 




20,500 


42 


M. 


A. 




Acute nephritis. 


15 


76 




20,400 




M. 






Cerebral embolism. 


16 


40 






20,000 


70 


M. 


















Double. 
















15,000 










Third day. 










10,400 










Seventh day. 


17 


45 




O O 4 4 AAA 

3,244,000 


19,900 


35 


M. 






No autopsy. 


18 


39 




19,700 


55 


M. 






With acute nephritis. 












Stenosis. 






19 


2o 







19,600 




M. 






Pulmonary infarction ; bloody pleurisy. 


20 


38 


M. 


3,648,000 


19,300 


45 


M. 






Albumin one-fourth per cent. 










Stenosis. 






21 


22 






19,000 




M. 






With nephritis. 


23 


35 






19,000 


72 


M. 






Broken compensation. 


23 


35 






18,000 




M. 








24 


9 







18,000 


ki\ 

DU 


M. 






First day. Temp., 19* °. 








4,160,000 


23,000 


oo 








Thirteenth day. 








30,000 


OO 








Twenty-second day. Hydrothorax. 


35 


54 






18,000 


65 


M. 






Temp. 98°. Died. 


26 


22 






17,900 


80 


M. 






27 


3C 






17,100 


DO 


M. 






No fever. 


28 


40 






16,800 


fin 
DO 


M. . 






Temp., 101°+. 


29 


64 






16,400 




M. 






Pulmonary infarction. 


30 


5 




3,808,666 


16,000 


45 


M. 






Temp., 99.0°. 


31 


34 






16,000 




M. 






First day. 










11,000 










Seventh day. Temp., 101°. 










21,000 


68 








Eighth day. 










14,200 










Fourteenth day. 










9,400 










Thirty-fifth day. 


32 


56 






16,000 


60 


M. 


A. 






33 


47 






15 400 




M 


A. 




TPTTin 99-100° 


34 


30 




3,920,666 


15'300 


38 


M.' 


a! 




First day. Temp., 99°. 








3,840,000 


8,600 


43 








Eleventh day. 








15,000 










Temp., 97°. 


35 


38 






14,100 


6.5 


"m." 




T. 




36 


27 






14,000 


100 


M. 


A. 


T. 


First day. 










13,000 










Third day. 


37 


49 






14,000 




"m." 


A. 




With diffuse nephritis. 


38 


58 






14,000 




M. 






Temp., 98°, with myocarditis. 


39 


34 






13,400 




M. 






Temp., 98°, with nephritis. 


40 


58 




3,814,666 


13,400 


50 


M. 


A. 




Temp., 98°. 


41 


50 




13,200 


55 


M. 








42 


19 




3,82b',666 


13,100 


55 


M. 








43 


52 




4,876,000 


12,800 


60 


M. 


A. 




Temp, usually subnormal. 



CONGENITAL HEART DISEASE. 325 



Table L. — Mitral Valve Disease and Its Complications {Continued). 













c 

G-S 


Lesions. 










Red cells 


White 
cells. 


§5 
^ be 
u o 






'^^ 


Remarks. 




• 
















6 




X* 








IMltrcil. 


Aonic. 








< 


0) 
















— 


21 






12,800 


• • 


M. 


A. 






45 
46 


28 
52 






12,800 
12,500 


60 
80 


M. 
M. 


A. 
A. 






47 


41 







12,100 


■ • 


M. 








48 


25 




4,480,000 


11.400 


45 


m! 


A. 




Temp., 98°. 


49 


46 




4,500,000 


11,200 


40 


M. 


A. 




With angina. 


50 


21 




11,200 


52 


M. 

Double. 






61 


48 






11,300 


65 


M. 








52 


68 






11,000 




M. 






Temp., 98°. 


53 


34 






11,000 


• • 


m! 






54 


33 






10,700 


65 


M 






Temp., 98°. 


55 


45 






10,600 


• • 


m! 


A. 




56 


54 






10,600 


73 


m! 






. 

Asthma. 


57 


43 






10,200 


77 


m! 






Broken compensation. 


58 


40 






9,900 




M. 


A. 




Temp, subnormal. 


59 


19 






9.900 




M. 






Temp., 98°. 


60 


lii 






9,900 
9,800 


• • 


M. 






61 


25 






70 


M. 


A. 






62 


40 






9,600 




m! 








63 
64 


38 
20 






9,600 
9,500 


70 


m! 
m! 

Double. 


A. 




Temp., 98°. Broken compensation. 
Temp., 100°. 


65 


o9 






9,400 


65 


M. 






Broken compensation. 


66 


54 






9,400 




M. 






Broken compensation. 


67 


'-*7 




o,dbU,OUU 


9,200 


inn 
iUU 


m! 






68 


49 




9,200 


• • 


M. 


A. 






69 


33 






9,000 


72 


m! 








70 


lil 






9,000 


• • 








December 14tn. 








6,452,666 


95 








December 21st. 


71 


61 




4,953,000 


8,900 


48 


M. 






Broken compensation. No autopsy. 
Temp., 98°. 


72 


49 






8,800 


60 


m! 






73 


46 






8,800 




m! 








74 








8,600 
8,500 




m! 


A. 




Fever. Gonorrhoea (?). 
lemp., 9<°. 


75 


46 








m! 




76 


40 






8,400 




M. 






Temp., 96°. 


77 


40 






8,2(X) 




M. 






Temp., 98°. 


7o 


QO 
OO 






8,000 




M. 


A. 






ITQ 

iv 


OO 






>7 arm 




m! 






Broken compensation. Temp., 97°. 


80 


41 






7,900 




M. 


















stenosis. 








81 


50 






7,800 




M. 






Temp., 97°. 


82 


44 




4,040,666 


7,500 


55 


M. 
















Double. 








83 


49 






7,300 




M. 








84 
85 


40 
oa 
40 






7,000 
6,800 




M. 

m! 








86 


32 






6,600 




m! 


















Double. 








87 


50 






6,000 




M. 








88 


30 




i,60o,o6o 


6,000 


10 


M. 


A. 




First day. Poly nuclear, 61 . 6 ; lympho- 




















cytes, 38; eosinophiles, 4; megalo- 
blasts, 1 ; normoblasts, 8 ; reds pale. 






































large, deformed. 








1,536,000 


4,200 


10 








Seventh day. Poly nuclear, 67; lym- 
phocytes, 32; eosinophiles, 1 ; megal- 
oblasts, 4; normoblasts, 7. Large 
oval forms. 








1,728,000 


10,400 


15 








Fifteenth day. 








1,720,000 


5,000 


12^ 








Twentieth day. Pol ynu clear, 71; 


















lymphocytes, 27 ; eosinophiles, 2 ; 
megaloblasts, 1. 




oi) 




1,840,000 


5,200 


18 








Tvi^enty -seventh day. 


89 




6.000 




'm." 


A. 




90 


40 






5,800 


76 


M. 






Temp., 98°. 


91 


40 






4,900 




M. 


A. 







326 SPECIAL PATHOLOGY OF THE BLOOD. 



Table LL— Aortic Valye Disease. 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


AO 






Oi.UUU 


^A 
OU 




KO 
04 






1 O AAA 


ftA 


rirstaa}. lenip., lUi . 








OA AAA 




Thivrl r^a\^ Tomi-i 1 A9° 
-LllllQ lla> . icllip., iU/& . 








26,000 




Sixth day. Temp., 102°. 








9^ OAA 




XilliULil Q<i> . lemp., iUi . 








30,000 




Fourteenth day. Temp., 101°. 








21,600 




Twentieth day. Temp., 99.3°. 












Twenty-seventh day. Autopsy. 


56 






7.800 




Angina. 


24 




5,024,000 


6,800 


60 




37 




6,000 




With chronic diffuse nephritis. 


24 






5,000 




78 






3,200 




Temp., 98°. 


22 




4,400,000 




45 





Tlie most important practical deduction from these data is that 
a blood count in a patient suffering from poorly compensated heart 
disease has no value in determining whether or not anaemia is pres- 
ent. The actual number of corpuscles in the body is not measured 
by the number contained in a drop of peripheral blood, since anae- 
mia may be effectually masked by concentration or simulated by 
dilution. 

This holds good equally for any condition involving general 
stasis and cyanosis either from embarrassment of the heart's action 
or otherwise (for instance, pneumonia in certain stage, emphysema, 
displacement of the heart by serous effusions, or tumors), or local 
stasis of the part from which blood is taken. Penzoldt^ noted that 
in old hemiplegic cases the blood from the affected side contained 
more corpuscles than that from the sound side, and the writer has 
noticed the same thing in a variety of vasomotor affections involving 
local asphyxia. 

ANEURISM. 

As a rule I have found the blood entirely normal, but in the fol- 
lowing case it might have thrown light on the diagnosis. A patient 
was recently admitted to the Massachusetts General Hospital with 
an acute affection of the chest, supposed to be pneumonia in spite of 
the slightness of the fever and the irregularity of the physical signs. 
At autopsy a ruptured aortic aneurism was found. The blood count 
had showed 3,324,000 red cells, 20,800 white, and 33 per cent 
iBerUner klin. Woch., 1881, p. 457. 



ACUTE NEPHRITIS. 



327 



hsemoglobiii. The low percentage of hsemoglobin and red cells was 
really inconsistent with, an acute pneumonia in a man previously 
well, and might have hinted strongly toward the correct diagnosis 
had attention been directed more carefully to the blood. After 
gelatine injections^ leucocytosis always appears. 

DISEASES OF THE KIDNEYS. 

Many factors other than the disease itself may influence the 
blood of nephritic cases. For instance, in scarlatinal nephritis the 
long-standing leucocytosis is probably due largely to the scarlatinal' 
poison, rather than to the nephritis. The occurrence of large quanti- 
ties of blood in the urine has the same influence as any other hem- 
orrhage upon the blood. 

(Edema as such has apparently very little effect upon the blood, 
but the loss of albumin in the urine tells both on the corpuscles and 
on the serum, thinning both with consequent lowering of the specific 
gravity of the blood. 

ACUTE NEPHRITIS. 

1. Red Cells and Hcemoglohin. 

Whether largely from the loss of blood from the kidneys or from 
other causes, the red cells are often much diminished, but the hae- 
moglobin suffers still more. 

H^MOGLOBINUEIA. 



Age. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


31 


3,428,000 


14.800 


40 


With CE 


sophageal symptoms. 



Laache reports an average loss of nineteen per cent of the red 
cells and twenty-six per cent of their coloring matter. 

Hayem found no considerable loss of red cells unless the urine 
was hemorrhagic. The following cases illustrate his results: 

Case I. — Acute nephritis, ending in recovery. 



Red cells. 

March 17th, 1882 3,069,000 

March 31st, 1882 2,759,000 

April 7th, 1882 2,821,000 

May 1st, 1882, albuminuria ceased. 

May 17th, 1882 3,038,000 

May 31st, 1882 3,689,000 



328 



SPECIAL PATHOLOGY OF THE BLOOD. 



Case II. — Acute (puerperal) nephritis ; recovery. 



Red cells. 

April 6tli, 1881 2,945,000 

" 9th, 1881 2,976,000 

" 12th, 1881, no albumin in urine. 

" 13th, 1881 3,137,500 

" 20th. 1881 3,310,000 

Case III.— Nephritis (chronic?) with hsematuria. 

Red cells 2,821,000 



(It should be noted that Hayem's counts are low on the average, 
and the instrument used by him was not very reliable.) 

Grawitz in acute nephritis records 3,400,000 red cells at the 
beginning of the third week, and 3,100,000 ten days later. 

Koblank^ counted 5,168,700 in a case of acute nephritis with 
oedema. 

Sadler {loc. cit.) in six cases of acute nephritis found in two 
cases 3,590,000 and 2,262,000 red cells; in the other four practi- 
cally normal counts. 

Table LII. — Acute Nephritis. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


18 mos. 






36,000 




Parenchymatous. 


56 


F. 




22,000 




Temperature, 102.5°. 








14,000 




Sixth day. 








11,900 




Ninth day, temperature falhng. 








12,200 




Nineteenth day. 


54 






16,850 


70 


24 




4,020,000 


14,000 


60 




11 


F. 


4,068,000 


14,000 


52 




45 


M. 


3,532,000 


13,200 


43 




40 




4,880,000 


12,700 


65 




40 






12,600 


75 




13 


F. 




12,000 






11 






11,800 


70 




23 


M. 




11,700 


50 




35 






11,500 


85 




24 


F. 




11,100 


85 








5,228,000 


10,800 


50 




33 


M. 


3,904,000 


9,300 


50 


Purpura also. 


22 


M. 


4,300,000 


8,300 


48 




22 


M. 


7,600 


60 




44 


F. 




7,500 


65 





' Inaug. Dissert., Berlin, 1889. 



CHRONIC PARENCHYMATOUS NEPHRITIS. 329 



Table LIL— Acute Nephritis {Continued). 



Age. 


Sex. 


Red cells. 


White 
cells. 


"Ppr* npnt" 

haemo- 
globin. 


Remarks. 


37 


M. 




6,800 


78 




25 




4,080,000 


6,600 


40 


Parenchymatous. 


55 






6,200 






20 






6,200 




Parenchymatous. 


20 


M. 


5,000,000 


6,000 


58 


Acute parenchymatous. 


22 


F. 


4,044,000 


5,400 








5,100 




Acute parenchymatous. 


20 




4,090,000 


5,100 


55 


39 




3,752,000 


65 





In none of the few eases examined at the Massachusetts General 
Hospital were the red cells much diminished, but in two cases the 
haemoglobin was very low, the color index being .62 in one and .61 
in the other. 

The blood plates are much increased (Hayem) and fibrin is 
slightly increased. 

2. White Cells. 

Leucocytosis is usually stated to be the rule, lasting often for 
weeks at a time and gradually diminishing in convalescence. 

Hayem gives counts of 14,973, 12,400, 15,000, and 13,000. 

Koblank (loc. cit.) and Grawitz each in a single case found 7ior' 
mat counts (7,300 and 5,600). 

Sadler found an increase in only one of his six cases, and then 
the highest point reached was 13,312. 

Of the twenty-six cases of Table LIT., leucocytosis was present 
in seventeen, in one of which it was followed for three weeks and 
still persisted ; but it is my OAvn belief that the leucocytosis of acute 
nephritis is due either to loss of blood by the kidney or to ursemia. 
When these conditions have been absent I have not found any 
leucocytosis. 

CHRONIC DIFFUSE AND CHRONIC PARENCHYMATOUS 
NEPHRITIS. 

Red Cells. 

In advanced stages the counts may run very low, but more often 
it is chiefly the haemoglobin that suffers through the drain of albu- 
minoids from the blood into the urine. 



330 



SPECIAL PATHOLOGY OF THE BLOOD. 



Hayem gives the following figures : 

Case I. — Chronic parenchymatous nephritis. 





Red cells. 


Per cent haemoglobin. 


June 20th 


4,309,000 


43 


July 4th 


4,216,000 


44 


October 18th 


2,945,000 


34 


Case II. — Same diagnosis. 






Red cells. 


Per cent haemoglobin. 


March 6th 


2,619,500 


36 


8th 


2,836,500 


36 


" 23d 


2,464,500 


27 



Koblank {loc. cit.) in the same disease found 3,291,700 red 
cells in a single case with much oedema. 

Eeinert found 4,050,000 with 50 per cent of hsemoglobin and 
8,604,000 with 62 per cent of hsemoglobin. 



Case 1 4,120,000 

( 2,405,000— November 19th. 
" 2 \ 1,100,000— January 14th. 

( 1,500,000— January 17th. 

" 3 4,300,000 

" 4 4,300,000 

( 3,737,500— June 28th. 
" 5 \ 3,593,700— July 3d. 

( 2,187,500— August 15th. 
3,200,000— July 7th. 
" 6 \ 3,257,000— July 22d. 

( 3,137,000— August 21st. 



Grawitz in an acute exacerbation of a chronic parenchymatous 
nephritis found 1,928,000 red cells. 

The Massachusetts General Hospital cases show a considerable 
ansemia in nine out of the thirty-six, or one-quarter of the series. 
Great concentration is probably the cause of the very high counts in 
certain cases. The majority of cases are not far from normal so far 
as the number of red cells goes, and the hsemoglobin is also very 



little diminished. 

Chronic Nephritis. 

Red cells. Cases. 

Between 1,000,000 and 2,000,000 1 

2,000,000 " 3,000,000 2 

3,000,000 " 4,000,000 11 

4,000,000 " 5,000,000 13 

5,000,000 " 6,000,000 6 

6,000,000 " 7,000,000.... 3 

Color index averages about .7. 36 



CHRONIC PARENCHYMATOUS NEPHRITIS. 



331 



White Cells. 

Hayem records 25,000, 19,000, 13,000, 10,000, and 6,000, and 
concludes that the counts vary much not only in different cases, but 
in the same case at short intervals. » 

Koblank found 14,700 in a single case. 

Sadler in one case found 6,300 in November and 16,000 in the 
following January; 12,000 in another case; 8,800, 7,700, and 
1,916 in others. 



Table LIII., A. — Counts in Chronic Kephritis with Uremia. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hEemo- 
globin. 


Remarks. 


32 


F. 




44,000 




Eclampsia. 


35 






25,000 




Coma first day. 








9,000 




Clear twc4ftli day. 


29 


F. 




22,600 




21 




4,080,000 


20,400 






29 




18,900 


80 


Temperature, 102.5°. 


29 


M. 




18,650 




Polynuclear, 83^. 


35 


F. 




18,600 




Coma five weeks after miscarriage. 


35 






18,000 




November 21st, arterio-sclerosis. 








15,800 




November 23d. 






4,184,000 


18,100 


60 


December 2d. 






2,320,000 


16,800 


18 


January 4tli. 


18 






17,800 


81 






5,236,000 


17,450 


52 


Eclampsia. 


49 


F. 




16,800 






33 






16,300 




Chronic diffuse. 


36 




4,650,000 


16,300 


58 


Polynuclear, 86.7^. 












Lymphocytes, 13.3. 












No nucleated reds or deformity. 


25 




3,604,000 


16,200 


50 


Chronic diffuse. 


20 


F. 




15,800 




Differential count normal. 


32 






15,800 




Chronic diffuse. Eclampsia. 


53 






15,000 












13,200 






38 


M. 




15,000 






45 


M. 




15,000 






35 






14,300 


70 


Chronic diffuse. Died in one month. 


37 


M. 




14,200 






15 


F. 




13,800 






25 


M. 




13,400 






13 




2,360,000 


12,800 


44 


Polynuclear, 77^. 








Eosinophiles = 0. 


23 


M. 




12,500 






58 


M. 




12,400 






58 






12,400 


60 




50 


F. 




12,300 






19 




3,104,000 


12,200 


35 


Chronic diffuse. 


59 


ii. 


12,100 






9 






11,900 




Interstitial. Asthma. 


63 






11,400 







332 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table LIII., A. — Counts in Chkonic Xephritis with Uraemia 

{Continued). 



Age. 


Sex. 


T?pr1 f*pll« 


White 
cells. 


Per cent 
srlobin. 




44 


M. 




11.300 






31 


M. 




11.200 






48 




3,448,000 


9,800 


35 




44 




8,400 


100 




31 




3,500,000 


7.500 


30 




45 


F. 


6.600 






34 


F. 




4.600 






30 


M. 




4,200 







Table LIII., B. — Chbonic Diffuse and Chronic Parenchymatous 
Nephritis. Xo Ur.emia. 



Age. 


Sex. 


White cells. 


Age. 


Sex. 


White cells. 


Age. 


Sex. 


White cells. 


26 




24,700 


17 


M. 


10,400 


28 


M. 


7,600 


55 




23,200 


50 




10.300 


25 


M. 


7.600 


21 




19.000 


43 


F.' 


10.300 


17 


M. 


7,500 


55 




18,500 


20 




10.200 


55 


31. 


7,400 


51 




18,000 


28 




10,100 


34 


M. 


7,400 


45 


ii 


16.300 


52 




10,000 


50 


F. 


7.300 


11 




16,000 


60 




10,000 


26 




7,300 


66 




15,800 


20 


F.' 


10,000 


28 


ii. 


7.000 


43 


M. 


14,500 


52 


F. 


9,800 


43 




7,000 


19 




14,300 


30 




9,500 


41 


M. 


6,800 


56 


R 


14,000 


25 




9,000 


8 


M. 


6,800 


66 


M. 


14,000 


24 


F." 


9,000 


8 


31. 


6,500 


47 




13,100 


36 




8,800 


39 


31. 


6.500 


27 


M. 


13,000 


54 




8,700 


7 


31. 


6,400 


11 


M. 


13,000 


45 




8,300 April 5th 


20 


F. 


6.250 


38 




12.800 April 4tli 






13,000 


41 


31. 


5,500 






13,900 April 6tli 






April 9th. 


43 




5,500 






28,650 


30 


M. 


8,300 


30 


F.' 


5,200 






April 9th, died. 


27 


F. 


8.300 


27 


31. 


5,100 


16 


F. 


12.700 


58- 




8.200 


30 


31. 


5.000 


48 




11.200 


16 




8,100 


58 


31. 


4,800 


25 


m". 


11.200 


56 




8,100 


30 


31. 


4.500 


10 


F. 


11.000 ! 


33 


m". 


■ 7,900 


41 


31. 


3,000 


47 


F. 


10.800 


14 


M. 


7,750 


25 




1,400 


56 


M. 


10.700 


15 


F. 


7,700 


i 







Tlie same wide range is seen in Table LIII., A and B, in which 
I have divided the urseniic and the non-ursemic cases into se^^arate 
tables. It will be seen from these that thirty-four out of forty 
ursemic cases showed leucocytosis, while thirty-nine out of sixty- 
nine non-ursemic cases showed no leucocytosis. It is difficult to 
suppose that this is mere coincidence. 



CHRONIC INTERSTITIAL NEPHRITIS. 



333 



CHRONIC INTERSTITIAL NEPHRITIS. 

Hayem found the fibrin more increased in this form of nephritis 
than in any other, and the anaemia less pronounced. 
Grawitz distinguishes two stages : 

I. As long as the heart is strong enough to overcome the 
increased resistance at the periphery and the disturbances of circu- 
lation are not marked, the blood is normal. 

II. When compensatory hypertrophy is no longer sufficient to 
do the work of forcing the blood through the system, the usual 
effects of failing compensation (see Heart Disease, page 320) appear 
(dilution and subsequent concentration of the blood) . 

The ivhite cells are normal. 



Table LIV.— Chronic Diffuse Nephritis; No Uremia. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


20 




3,492,000 


39,000 


42 


With bronchitis. 


26 




3,500,000 


26,300 


50 


With acute articular rheumatism. 


36 




2,560,000 


16,100 
12,400 


35 
20 


April 14th. 
April 30th. 








8,900 




May 1st. 


37 




3,144,000 


16,000 


40 


11 




3,660,000 


15,600 


52 




33 




3,568,000 


14,600 


45 




22 




4,272,000 


14,400 


45 


Sub-acute. 


19 




5,864,000 
6,092,000 


14,300 
13,700 


65 


Amyloid liver and spleen. February 

12th. 
From ear. 






5,740,000 


13,700 




From finger. 


24 




3,824,000 
4,268,000 


11,400 
13,600 


55 


16 




3,724,000 


11,300 


45 




35 




3,164,000 


10,600 


50 


Tertiary syphilis. 


42 




4,228,000 


10,100 


65 


(Edema. 


19 




3,776,000 


10,000 


516 


Cardiac hypertrophy. 


28 




4,560,000 


10,000 


45 


47 




4,450,000 


9,800 


50 




21 




4,080,000 


8,600 


70 




42 




3,416,000 


7,000 


55 




55 




4,360,000 


6,300 


50 


Ascites. 


24 




4,800,000 


5,700 


65 




26 




1,468,000 


3,800 


23 


Polynuclear, lymphocytes, 23^; 
large lymphocytes, 4. 4^ ; eosinophiles, 
2.6^; reds, megaloblasts, 3; normo- 
































blasts, 2; microblasts, 1. Consider- 












able variation in size; many oval 
forms ; considerable poikilocytosis. 













334 SPECIAL PATHOLOGY OF THE BLOOD. 



Table LI V.— Chronic Diffuse Nephritis; No Uremia 
{Contimied). 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


36 




1,136,000 
1,752,000 
2,248,000 
2,540,000 

3,392,000 
3,580,000 

5,060,000 


5,800 




19 
22 
30 
48 

60 
65 

75 


Polynuclears, 71.8^; ly mpliocy tes, 24. 2%; 
large lymphocytes, 2. 2^; eosinophiles, 
1.2^; myelocytes, 6; megaloblasts, 6; 
normoblasts, 3. November 5th. 

Polynuclears, 69.4^; lymphocytes, 
25.2^; large lymphocytes, 3.8^; eo- 
sinophiles, 1.6^; megaloblasts, 4; 
normoblasts, 2. November 13th. 

Polynuclears, 65.4^; lymphocytes, 28^; 
large lymphocytes, '6%; eosinophiles, 
3.4^; basophiles, 2; megaloblasts, 1; 
normoblasts, 0. November 20th. 

Polynuclears, 70.2^; lymphocytes, 23^^; 
large lymphocytes, 2. 6^ ; eosinophiles, 
3.4^; basophiles, .8^. Red variation in 
size and shape less marked. Megalo- 
blasts, 1. November 27th. 

December 6th. 

Polynuclears, 79^; lymphocytes, 17.6^; 
large lymphocytes, 1.8%; eosinophiles, 
1.6^. Reds stain well ; slight poiki- 
locytosis and variation in size; no 
nucleated reds. 

Hemorrhagic nephritis. 



Table LIV., A.— Chronic Interstitial Nephritis. 



6 
12; 


Age, 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


29 






23,700 


65 




2 


39 


M. 


6,040,381 


19,000 


80 


Urnemic coma; moribund. 


3 




F. 


4,548,000 


15,000 


50 


Urjemic ; mitral stenosis. 


4 


"63* 




3,872,000 


14,000 


55 


General paresis. 


5 


Adult 


M. 


4,244,000 


12,000 


67 


Three and one-half hours after a 










meal. 


6 


22 




5,020,000 


11,200 


50 




7 


46 


M. 


9,724 




Uraemic ; moribund. 


8 


47 






7,300 






9 


20 


M. 


4,088,000 


6,000 


66 


March 23d. 










52 


March 30th. 


10 


34 


F. 


3,536,000 


8,300 


57 




11 


69 


M. 




8,500 


87 




12 


32 


M. 




6,000 


65 




13 


60 






5,900 




With mitral disease. 



STONE IN THE KIDNEY. 



335 



PYELONEPHRITIS. 

Table LIV., B, speaks for itself. The ancemia is often severe 
and leucocytosis is the rule. 



Table LIV., B. — Pyelo-Nephritis. 



1 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


24 


F. 


3,056,000 


21,200 


41 


March 10th. Uraemia. 








2,976,000 


15,200 


38 


March 13th. 








2,696,000 


18,800 


33 


March 27th. 








3,272,000 


25,200 


33 


April 14th. 


2 


26 


F. 


4,200.000 


16,800 




Perinephritic abscess too. 


3 


33 


M. 


4,536,000 


15,550 


36 


Cystitis also. 


4 


26 


F. 


2,356,000 


7,280 


65 


Cystitis also. 


5 


40 






6,800 




Pyelitis. 



Table LIV., C— Cystic Kidney. 



6 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hserao- 
globin. 


Remarks. 


1 


55 


M. 


3,664,000 


6,400 




Adult cells, 72 per cent. Supposed 














cancer. Enormous firm tumor 














on each side. Autopsy. 



The cases recorded in Table LIV., A, are probably not incon- 
sistent with these rules. Of the seven cases with leucocytosis three 
were ursemic, and in a fourth the influence of digestion is seen. 
The haemoglobin is lower than we should expect from Grawitz's 
account. 

Urcemia, it would appear from these tables, may cause leucocy- 
tosis, or at any rate is not infrequently associated with it. Aside 
from uraemia and hemorrhage, nephritis probably does not cause 
leucocytosis. 

STONE IN THE KIDNEY. I 

'■ - :■ I 

(See Table LV., A.) The state of the blood depends on the 
amount of ulceration caused by the stone; when this is considerable 
we have leucocytosis. 



336 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table LV., A. — Stone in the Kidney. 



d 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Rem&rks. 


1 








22,800 


85 


Tender in loin. 










16,200 






2 


51 






16,500 




August 10th. 










10,800 




August 12th. Pain gone. 


3 


19 


M. 




15,200 




Much pus in urine. 


4 




M. 


4,350,000 


14,750 


78 


5 


53 






12,900 


73 




6 


20 






10,200 






7 


25 


F.' 


4,160,000 


9,000 


65 




8 


48 


M. 




8,990 






9 


58 


M. 


5,680,000 


8,000 






10 






4,340,000 


3,000 




Much pus in urine. 








6,100,000 


16,500 




Two weeks later. 


11 


52 


M. 


3,048,000 


7,500 


30 




12 


45 


M. 


7,500 


95 




13 


51 


M. 




6,000 


95 


Uric-acid stone passed. 


14 


30 


M. 




4,980 


85 



Diagnostic Value. 

Cancer would also cause leucocytosis, but would not increase 
fibrin as a rule, while most cases of stone with ulceration do increase 
fibrin. 

FLOATING KIDNEY. 

The blood is normal. This fact has some diagnostic value ; for 
example, when we confound appendicitis with floating kidney, as 
has been done (see page 247). The presence of leucocytosis ex- 
cludes the latter and favors the former. Most tumors or abscesses 
with which a floating kidney might be confused could be distin- 
guished by the same criterion. 



Table LV., B. — Floating Kidney. 





Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


47 




4,650,000 


23,000 

17,400 
21,300 
21,800 


45 


March 28th. Peritoneal inflamma- 
tion. 
April 4th. 
April 9th. 

April 15th. Dife. count 300. Poly- 
nuclear, 87 per cent ; small lym- 
phocytes, 7 ; large lymphocytes, 
5.5; eosinophiles, .5; reds aver- 
age size ; very few poikilocytes. 



BRONCHITIS. 337 



Table LV., B. — Floating Kidney {Continued). 



1 


Age. 


Sex. 


Red cells. 


White cells. 


id LCllu 

haemo- 
globin. 


Remarks. 


2 


65 




4,482,000 


11,800 


65 


Double. 


3 


24 






11,200 


70 




4 


37 


F. 


5,056,000 


9,200 


75 




5 


41 


F. 


4,684,000 


9,000 


75 




6 


24 


F. 




8,100 






7 


67 


F. 




8,000 


65 




8 


23 


F. 


5,400,000 


6,000 


69 




9 


43 


F. 


4,700,000 


2,400 


76 




10 


38 


F. 




75 


Aneurism of arch also. 


11 


24 


F. 






80 


12 


38 


F. 


4,416,000 


5,800 


67 




13 


24 


F. 


7,600 


80 





A large number of similar counts might be quoted. 



HYDRONEPHROSIS. 



Table LVI., C— Hydronephrosis. 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Remarks. 


52 




4,016,000 


16,400 


75 


March 7tli. 






10,800 




March 12th. 


4 




5,496,000 


14,300 


60 








28,600 




Operation. Congenital. 



PYONEPHROSIS. 

Case I. — Female, 36; leucocytes, 16,200, of which 85 per cent 
are neutrophiles. Half a pint of pus found at operation. 

Case II.— July 25th— Red cells, 3,856,000; white cells 9,800; 
haemoglobin, 45 per cent. July 9th — Red cells, 3,450,000; white 
cells, 9,000; haemoglobin, 55 per cent. August 3d — White cells, 
6,650. August 6th — Operation. Pint of foul pus. Death. 

DISEASES OF THE LUNGS. 
BRONCHITIS. 

"Acute catarrhal and chronic purulent bronchitis have rela- 
tively little leucocytosis in most cases'' (v. Limbeck). 

Except for this and a few other passing references, there is 
hardly anything in literature on the blood in bronchitis, so that I 
shall be forced to base my statements chiefly on the few counts 
recorded at the Massachusetts General Hospital. 
22 



338 



SPECIAL PATHOLOGY OF THE BLOOD. 



ACUTE BRONCHITIS. 

Aside from " capillary bronchitis, " cases are not infrequently 
seen in which the signs are simply those of general bronchitis of the 
finer tubes, yet the symptoms are much more like pneumonia. 
Whatever may be the real conditions in the lungs of such patients, 
their blood is not infrequently exactly like that of pneumonia and 
does not help at all in the differential diagnosis between the two 
disease (see Cases 1 and 2, Table LVI., A). 



Table LVI., A. — Acute Bronchitis. 



Sex. 



Red cells. 



White cells. 



Per cent 
hasmo- 
globln. 



Remarks. 



5,808,000 



4,420,000 
4,800,000 



5,660,000 



F. 



M. 



4,192,000 



6,196,000 



45,000 
26,400 
68,800 
41,000 
26,000 
26,000 
25,900 
17.100 
25,750 
28,500 
23,450 
22,200 
21,200 
20,400 
20,100 
19,100 
19,000 
19,000 
17,200 
17,000 
15,000 
15,100 
15,000 
11,300 
17,600 
15,000 
14,200 
13,800 
16,300 
16,400 
13,000 
13,000 
12,600 
11,800 
6,600 
12,600 
12,000 
12,000 



58 



70 
65 

67 



80 
67 



58 



62 



65 



70 
60 



Fourth day. 
Eleventh day 



died. 



65 



Temperature, 103°. 
Whooping cough. 
Temperature, 101°. 
Fourth day ; well. 
Subacute; temperature, 99°. 
With enteritis ; temperature, 108° 
Temperature, 101°. 
Temperature, 101°. 
Temperature, 103°. 

Temperature, 103°; asthma. 
Temperature, 100°. 
Temperature, 99.5°. 
Temperature, 98°. 
Subacute. 

First day ; temperature, 100°. 

Four days later, temperature, 98° 

Temperature, 103°. 

November 5th. 

November 16th. 

November 25th. 

Subacute; temperature, 100°. 

Temperature, 101.5°. 

Temperature, 102°. 

Third day. 

Sixth day. 

Temperature, 100°. 

Temperature, 102.5°. 

Third day; temperature, 101° 

Sixth day; temperature, 100°. 

Eleventh day ; temperature, 98°. 

Temperature, 101.5° 

Temperature, 102°. 



ACUTE BRONCHITIS. 
T.^LE LVI., A. — Acute Bronchitis {Continued). 



339 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 

tijemo- 

globin. 


Remarks. 


46 


M. 




11.800 




Temperature, 104°. 


13 






10.800 




Temperature, 102°. 


20 


M. 




10.600 


65 


Temperature, 104°. 


40 


M. 




10,300 




Temperature, 101°. 


31 






10,200 




Temperature, 102°. 


69 






9,400 




Temperature, 101°. 


43 


M. 




9,300 




50 


F 


5,260,000 


8 000 


72 




50 


M. 


5^952,000 


7^900 


50 




38 




7,800 




Temperature, 99°. 


48 






7,800 




Temperature, 102°. 


25 






7,200 




Temperature, 100°. 


52 


M. 




7,000 


70 


25 


31. 




7,000 


74 


Temperature, 103°. 


56 


F. 




6,800 




36 


M. 


4,392,000 


6,000 


72 


October 31st. 






8,600 




November 3d. 


43 






5.900 




Temperature, 100°. 


29 


M. 




4,000 


80 


Temperature, 102°. 



T.VBLE LVI., B.— Chronic Bronchitis. 



2 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
heemo- 
globin. 


Remarks. 


1 


51 






38,000 






2 


24 






29,500 






3 


Adult 


M. 


3,680,000 


18.500 


63 




4 


68 






16.400 




With emphysema. 


5 


48 


M. 




15,000 




Chronic febrile, with laryngitis. 














Recovery. 


6 


64 






15,000 




Temperature, 98.6°. 


7 


62 






14,300 




Temperature, 100°; with asthma. 


8 


65 






12.900 




Fibrinous. 


9 


60 






10.500 






10 


43 






11,000 




Temperature, 98°; chronic with 














emphysema. 


11 


74 






8,900 




Temperature, 98°. 


12 


27 


F. 


5.384,000 


8,800 


73 


Constipation ; neurasthenia ; two 














weeks afebrile. 


13 


61 


M. 


4,300,000 


8,000 


63 


Five months. 


14 


20 


F. 




7,925 


78 




15 


18 


M. 




7,792 




Keratitis, conjunctivitis. No 














symptoms. 


16 


26 


F. 


4,700,000 


6.700 


70 


Asthma. 


17 


29 


F. 


4,100,000 


5,500 


61 


Empyema of the antrum. 


18 


20 


M. 


5.062 




One month. 



340 



SPECIAL PATHOLOGY OF THE BLOOD. 



In the majority of acute cases, however, the blood shows uo 
changes unless concentration clue to cyanosis be present. 

In chronic cases (Table LYI., B) leucocytosis is very uncommon; 
more so, I think, than the table represents. If more counts were 
added, nearly all, I think, would be normal. 

The red cells and haemoglobin show no changes to speak of m 
either acute or chronic cases. 

The blood has no diagnostic value so far as I know except that 
when pneumonia is in question a normal count of white cells speaks 
against it and in favor of bronchitis. If emphysema is also present, 
it sometimes produces a condition of the blood different from that 
in simple bronchitis. 

EMPHYSEMA AND ASTHMA. 

Grawitz reports an increase in the number of red cells in em- 
2oliysema, which he believes to be due to cyanosis, and this covers 
up the really anaemic condition of the blood of many patients. 
Practically the same conditions are present as in the cyanosis 
of heart disease (see page 320) and the concentration of the blood 
is brought about in the same way. Leichtenstern^ noticed a 
diminution in haemoglobin at the time when the heart first fails, 
due probably to the diminished blood pressure which allows the 
lymph from neighboring tissues to flow into the vessels and dilute 
the blood. 

In both asthma and emphysema it has been noted by Mtiller,"^ 
Gollasch,^ Gabritschewsky* and others that eosino2:)hUes are very 
numerous in the sputum, and Fink" also noted an increase of the 
same cells in the blood, running as high as 14.6 per cent instead 
of the normal one to two per cent. This increase is present onl}^ 
at the time of the paroxj^sm and for a short time before and after 
it. Yon Noorden found in one case 25 per cent of eosinophiles 
during an attack, and a few days later could discover but one eosin- 
ophile in twelve cover slips. In another case, after five attacks on 
successive days, the eosinophiles were 33 per cent. Billings^ reports 
the following counts : 

1 "Ueber das Hb-Gehalt des Blutes," etc., Leipzig, 1878. 

2Ref. in Fink, "Beitrage z. Kennt. des Eiters, " Dissert., Bonn, 1890. 

3 Fortschritte der Med., 1889. 

^ Arch. f. exp. Path, und Pbarm., 1890, p. 83. 

5 New York Med. Journal, May 22d, 1897. 



EMPHYSEMA AND ASTHMA. 



341 





January 26th, 


February 4th. 


February 11th. 




^ Q11 nnn 




1, OoU, uuu 




8,300 


7,500 


7,600 




68 per cent. 


75 per cent. 


86 per cent. 


Polymorp honuclear 






cells 


36 






Lymphocytes (small) . . 


5 






Lymphocytes (large) . . 


5.2 " 






Eoslnophiles 


53.6! " 


38.2 per cent. 


33. 9 per cent. 


Few normoblasts 




No nucleated 








red cells. 



Their presence in increased numbers before a paroxysm is said to make 
it possible to predict its coming (v. Noorden, Schwerskewski). Coler 
reports a case of asthma with a leucocytosis of 52,000, 25 per cent 
of which was made up of eosinophiles. The case was complicated 
with extensive purpura, painful muscles, and extreme cyanosis, but 
microscopic examination of the affected muscles showed no trichinae. 

I have watched one subacute case without well-marked parox- 
ysms or periods of perfect health. The blood was frequently exam- 
ined and showed always a slight leucocytosis with 11 to 15 per cent 
of eosinophiles. As this applies only to pure hroyichial asthma and 
not to cases secondary to disease of the heart or kidney, Schreiber 
states that we are enabled to distinguish bronchial from cardiac or 
renal asthma by the increase of eosinophiles in the blood and sputa 
in bronchial cases, which does not occur in asthma due to cardiac 
and renal trouble. Other records are (Gabritschewsky) : 



Case I.— White cells 8,200 

Eosinophiles 10.8 per cent. 

Case II.— White cells 6,800 

Eosinophiles ; 22.4 per cent. 

Polynuclears 35 " 



Asthma. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


26 


M. 




32,500 

19,200 
19,800 

13,000 
9,750 




Fifth. Temperature 100°. Bron- 
chitis and emphysema. 

Seventh. Temperature normal. 

Typical bronchial asthma during 
paroxysm. 

Chronic asthma and emphysema in 
paroxysm ; polynuclear cells, 79 
per cent. 


50 


F. 




50 


70 
29 


M. 
M. 


5,500,000 









342 



SPECIAL PATHOLOGY OF THE BLOOD. 



For Pneumonia, see page 189. 

For Phthisis, see page 271. 

For Abscess of Lung, see page 252. 

SYPHILIS OF THE LUNG. 

In a case of syphilitic infiltration of the lung (autopsy — Drs. 
Councilman and Wright) recently observed at the Massachusetts 
General Hospital the leucocytes rose rapidly from 8,700 to 27,400 
as death approached. 



Gangrene of Lung and Abscess. 



Age. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


49 




39,900 




Abscess, autopsy. 


42 




22,400 




Abscess after grippe. 


19 




18,400 




Gangrene. 


48 




16,400 




Abscess after immersion. 


54 




15,300 




First day. Gangrene. 






20,500 




Fourteenth day. 






18,300 




Sixteenth day. 






23,000 




Nineteenth day. 






27,000 




Twenty -first day. 






27,000 




Twenty-sixth day. 






31,000 




Twenty-ninth day. 






17,000 




Thirty-second day. Better. 






20,000 




Thirty-sixth da)'. 






15,800 




Fifty-fourth day. 


50 




9.600 




Gangrene. 



PART Y. 



DISEASES OF THE NERVOUS SYSTEM, CON- 
STITUTIONAL DISEASES, AND HEMOR- 
RHAGIC DISEASES 



CHAPTER VIII. 

DISEASES OF THE NERVOUS SYSTEM. 
NEURITIS. 

In cases of multiple neuritis, febrile and apparently of an infec- 
tious nature, the following counts are found in the records of the 
Massachusetts General Hospital : 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
hgemoRlobin. 


Remarks. 


24 




4,816,000 
4,320,000 


25,000 
24,800 
18,700 
21,000 
16,000 
28,700 
19,500 
23,200 
8,400 

6,400 


42 
60 


July lOtli. Temperature, 101°. 
July 13th. 
July 16th. 
July 20th. 
July 25th. 

July 31st. No fever. 
August 7th. No fever. 
August 20th, No fever. 
Polynuclear, 36^. 
Lymphocytes, 62^. 
Eosinophiles, 2. 
(Count, 300 cells.) 


22 

















The first case, a boy of eleven, recovered and left the hospital 
well. 

But these changes occur also in alcoholic (afebrile) neuritis, as 
the following counts show : 



344 SPECIAL PATHOLOGY OF THE BLOOD. 



Age. 
_ — 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


: 

Remarks. 


40 






16,100 




Pneumonia. No autopsy. 






8 fi08 000 


15,000 


i o 






3,260,000 


14^000 


64 










13,700 


60 




39 




3,584,000 


12,000 


45 










11,200 


68 










7,700 


80 




25 






7,600 












6,700 


82 





In all cases the counts were made just at meal time, so that the 
leucocytosis is not due to digestion. Gastritis was not present in 
either case. 

One case of post-diphtheritic neuritis in a child of eight showed 
the presence of ansemia only: Eed cells, 3,850,000; white cells, 
7,393; haemoglobin, 70 per cent. 

Neuritis in lead poisoning does not affect the count of leuco- 
cytes, as twenty-five cases studied at the Massachusetts General 
Hospital have shown. 



Herpes Zoster. 



No. 


Age. 


Red cells. 


White cells. 


Per cent 
hgemoglohln. 


Remarks. 


1 


52 




15,500 




Temperature 99°. 


2 


74 




9,100 






3 


53 




8,500 


60 





Neuralgia, whether facial, intercostal, sciatic, or ovarian, showed 
normal blood in numerous cases examined at the Massachusetts 
General Hospital. 



DISEASES OF THE BRAIN. 

Meningitis (see Inflammation of Serous Membranes, page 266). 

Zappert in one case of brain abscess found only 4,000 white cells. 

In pachymeningitis hcemorrhagica and cerebral syjyJdlis (one case 
of each) v. Jaksch found leucocytosis. My own experience has been 
the same. 

Cerebral and cerebellar tumors have no effect on the blood as far 
as could be judged from nine counts in the former and three in the 
latter disease. Von Jaksch found slight leucocytosis in two cases 
of brain tumor and one of cysticercosis. Zappert found normal 
blood in one case of cerebral tumor. 



DISEASES OF THE BRAIN. 345 



Table LVII. — Cerebral Tumor. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hasino- 
globln. 


Remarks. 


43 








18,100 


70 




OO 






1 A QAA 


'7K 
iO 




22 






15,000 






13 






14,500 
13,700 






26 






12,500 






4 






12,200 


70 




27 






10,600 


60 




33 






9,000 


72 




52 






7,000 






31 






4,100 







Fresh cerebral hemorrhage usually causes leucocytosis, as the 
following table shows : 



Table LVIII. — Cerebral Hemorrhage. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


42 


M. 




31,000 


95 


Autopsy. 




M. 




30,000 




Polynuclear cells, 92^^. 






C P: i AAA 

5,512,000 


25,000 


85 


Autopsy. 


bO 






29,700 




Autopsy. 


60 






23,600 










26,000 




Second day. 


55 






22,200 




Coma. 


69 






19,800 






47 


M. 




19,400 




Autopsy. 


54 






19,000 


65 


56 






17,400 


100 


Coma. Hemiplegia. 


70 


F.' 




16,800 


68 


Hemorrhage four daj^s before count. 












Autopsy. 






5,560,000 


15,600 


90 


59 




16,000 






62 






14,900 




Temperature, 104.7°. Died. 


52 






13,800 




Hemiplegia. Died. 


48 






13,000 




Hemiplegia. Coma. 


37 


M. 




12,300 


70 


68 






12,000 












11,900 




No coma. 


55 






11,800 






42 






11,600 






38 


M. 




10,400 


58 


Conscious ; recovered. 


37 


M. 




10,300 


90 


Autopsy. 


65 


M. 




10,200 


60 


60 






10,200 


70 




65 




952,000 


5,200 


18 


Arterio-sclerosis ; emphysema of 












lungs ; pernicious anaemia. Tem- 












perature, 102". 












Polynuclear, 84.2^. 












Lymphocytes, 13.8^. 












Eosinophiles, .8^. 












Myelocytes, .8^. 












Basophiles, .2^. 












Megaloblasts = 6. 



346 



SPECIAL PATHOLOGY OF THE BLOOD. 



CAISSON DISEASE. 
Age. White cells. 

18,900 

80 10.700 



CHOREA AND TETANY. 

Chorea showed in twelve cases normal blood except for increased 
percentages of eosinophiles, as in Zappert's four cases, counted 630- 
1,360 (8-19 per cent of eosins). 

Burr has made a careful study of the blood in thirty-six cases 
and arrived at the following conclusions : There is usually a slight 
diminution in red cells and a moderate diminution in haemoglobin. 
Any severe grade of anaemia is due to some complication. He did 
not record the leucocytes. Tetany shows no blood changes. 

DISEASES OF THE SPINAL CORD. 

Chronic diseases of the spinal cord, such as tabes dorsalis, syr- 
ingomyelia, spastic paraplegia, diffuse myelitis, paralysis agitans, 
and progressive muscular atrophy, are found to produce no changes 
in the blood. 

For Spinal Meningitis, see page 267. 

GENERAL PARALYSIS OF THE INSANE. 

Capps^ has made a careful study of the blood in nineteen cases 
and comes to the following conclusions : 

1. Red corpuscles and haemoglobin are always slightly dimin- 
ished, the averages being 4,789,900 and 85 per cent. 

2. Most cases show a slight leucocytosis — 22 per cent above 
the normal on the average. Early cases may have no leucocytosis. 

3. The dilferential counts show that the blood is slightly older 
than that of normal adults. The polymorphonuclear leucocytes 
average nearly 74 per cent and the smaller forms of lymphocytes 
only 14.2 per cent, while the larger forms of lymphocytes are rela- 
tively numerous, averaging 7.8 per cent. In a few cases the 
eosinophiles were very numerous^ (8.7 and 6.4 per cent). 

4. At the time of convulsions the red cells and haemoglobin are 

^ American Journal of the Medical Sciences, July, 1896. 
^Roncoroni (Archiv di Psichiat. Scien., 1894, p. 293) finds eosinophiles in- 
creased even to twenty-five per cent in the agitated and violent cases. 



HYSTERIA AND NEURASTHENIA. 



347 



apparently increased (due no doubt to the violent muscular contrac- 
tions which raise blood pressure and concentrate the blood, or to 
cyanosis) . 

There is a sudden and pronounced increase in the leucocytes 
during and after convulsions or apoplectiform attacks. That this 
is not due to concentration of the blood or to stasis, Capps thinks is 
shown by the fact that not only the number, but the differential 
count of white cells shows changes, the " large mononuclear " cells 
being relatively increased, sometimes as high as 25 per cent. Myelo- 
cytes were seen in one case after the con^oilsions, and especially just 
before death, when in a leucocytosis of 18,250 11 per cent were 
myelocytes.' 

HYSTERIA AND NEURASTHENIA: HYPOCHONDRIASIS. 

A large number of cases have been counted at the Massachusetts 
General Hospital, with a view of excluding other diseases. The 
blood count is always normal except that in a certain number of the 
hysterical cases eosinophiles are relatively increased, and that many 
of the neurasthenics show the increased percentage of lymphocytes 
which I have alluded to above (page 114) as characteristic of a vari- 
ety of debilitated conditions. 

Marked ancemia is seldom present, although the haemoglobin is 
not infrequently as low as 65 per cent. Eeinert'^ found the hsemo- 
globin under 60 per cent in only 4 out of 48 cases of hysteria, and 
in none of 36 neurasthenics. 

The value of the blood examination in such cases, like that of 
the urine or the lungs in hysteria, is as negative evidence, and in 
this respect it is important. When the discrepancy between com- 

^ Leucocytosis has been repeatedly noticed in convulsions from various 
causes. Probably the irritant wliicli causes the motor discharge also acts on 
the leucocytes by chemotaxis. For example Barrows' study of 8 cases of 
insanity with convulsions includes counts of — 1, 43,000 leucocytes with 92 per 
cent of polynuclears ; 2, 33,000 leucocytes with 83 per cent of polynuclears ; 3, 
32,400 leucocytes with 85 per cent of polynuclears and 9 per cent of myelo- 
cytes; 4, 21,500 leucocytes with 88 per cent of polynuclears. These counts 
were made immediately after a series of convulsions. The leucocytosis lasted 
for many hours and showed the characteristics of ordinary infectious leuco- 
cytosis. 

In convulsions from improper feeding in infancy I have seen the leuco- 
cytes rise from 13,500 before the tit to 27,800 after it. 
^Mlinch. med. Woch., 1805, No. 14. 



84S SPECIAL PATHOLOGY OF THE BLOOD. 

plaints and signs is great, we want to be doubly sure tliat nothing 
hidden escapes our notice, and the blood examination is one of the 
most valuable adjuvants we have in the discovery of deejo-seated 
inflammation or malignant disease, as well as in giving us a general 
measure of the patient's degree of bodily health as distinguished 
from nervous force. The former may be high when the latter is 
low, or both may be low, and the distinction marks out two classes 
of cases in which somewhat different treatment is appropriate. 
There is no use in undertaking to make " blood and fat " when the 
patient has already plenty of each, though it may be well to carry 
out the same regime as a matter of suggestion. 

MENTAL DISEASES. 

The association of anaemia with insanity is too frequent to be a 
mere coincidence, though it is hard to make either serve as a cause 
for the other. Very possibly they should both be looked upon as 
symptoms of a common underlying (unknown) cause. 

This form of anaemia has been noticed by Houston' in melan- 
cholia and general paralysis, and by Smith" in various forms of 
insanity. 

Krypiakiewicz^ noticed an increase of eosinophiles in acute forms 
of insanity, but not in the chronic forms. The leucocytosis of acute 
delirium^ is exemplified by the following case from the Massachu- 
setts General Hospital records : 

A girl of fifteen; acute delirium; leucocytes, 12,750; no food 
for eight hours; red cells, 4,510,000; haemoglobin, 63 per cent. 

Puerperal inania is to be distinguished from the delirium of 
puerperal sepsis by the fact that the latter shows leucocytosis with 
increased percentage of polymorphonuclear cells, while the former 
has no leucocytosis (if uncomplicated) and the eosinophiles are apt 
to be increased^ (diminished in sepsis). 

A case of puerperal mania seen by the writer showed : Eed cells, 
5,210,000; white cells, 6,500; haemoglobin, 84 per cent; eosino- 
philes, 8 per cent. 

^Houston: Boston Med. and Surg. Journal, January lltli, 1894. 

2 Smith: Jour, of Ment. Sci., October, 1890. 

^ Krypiakiewicz : Wien. med. AVoch., 1892, No. 25. 

■*Ref. in Klein-Volkmann's "Sammlung kiln. Yortrage," December, 1893. 
^Neusser: Loc. cit. 



DIABETES. 



349 



CONSTITUTIONAL DISEASES. 
OBESITY. 

Oertel distinguishes a plethoric and an anaemic form of obesity 
not merely clinically, but by the evidence of post-mortem examina- 
tions. He believes that there is a real over-filling of the vessels in 
the first. The second form occurs most often in women. 

Kisch examined (with v, Fleischl's instrument) the haemoglobin 
of 100 obese patients ; 79 showed over 100 per cent of haemoglobin, 
1 reaching 120 per cent, while the other 21 were anaemic. 

DIABETES. 

There is nothing characteristic about the blood except the in- 
creased amount of sugar to be detected (.57 per cent as against .1 
per cent normally) ; but this is not a clinically applicable test. 

Two simple tests for diabetic blood have recently attracted at- 
tention : 

1. Bremer's test : Heat thick-spread blood films to 135° C. ; cool 
and stain with one-per-cent aqueous solution of Congo red for two 
minutes. The blood if diabetic looks yelloic (to the naked eye). 
Normal blood similarly treated looks red. Staining with methyl 
blue also shows a difference between normal blood and diabetic 
blood. The normal is blue, the diabetic yellowish green. 

2. Williamson's test: Make a mixture of 

Blood 20 c.mm. (2 drops). 

Aqueous methyl blue (1 : 6,000) 1 c.c. 

Liquor potassae, 60 per cent (sp. gr., 1.058). . 40 c.c. 

Water 40 c.c. 

Let the mixture stand three to four minutes in boiling water. With 
diabetic blood the mixture turns yellow, with normal blood it does 
not. Williamson has found this test positive in eleven diabetics 
and negative in one hundred cases of other diseases. Bremer claims 
that by his method cases of diabetes can be recognized before sugar 
appears in the urine or after it has (temporarily) disappeared. Le 
Goff confirms the value of the test. Eichner and Eolkel find 
Bremer's reaction to be as stated, but find similar color changes in 
leukaemia, Hodgkin's disease, and Graves' disease, and changes 



350 



SPECIAL PATHOLOGY OF THE BLOOD. 



something like it in a variety of cachectic conditions. Badger has 
studied the blood of diabetics, leuksemics, cases of Graves' disease, 
and other cases at the Massachusetts General Hospital. Only in 
Graves' disease did he find reactions like those of diabetic blood. 

The alkalinity has been said to be greatly diminished, especially 
in the fatal coma, but v. Noorden thinks the tests are unreliable. 

Fat is often increased in the blood, up to about twelve times the 
normal, so that the serum is milky, and glycogen has been demon- 
strated microchemically in the corpuscles. 

Red Cells. 

Sugar in the blood draws water from the tissue into the vessels, 
thereby diluting the blood ; but in a short time the blood frees itself 
of the excess of sugar and fluid through increased diuresis so as to 
concentrate the blood. 

These two alternating influences serve to explain the widely dif- 
ferent counts of different observers. 

Toward the end of the disease a decided cachexia often develops, 
the ansemia of which may be temporarily covered up by the concen- 
tration above noted, or accentuated by the dilution which sometimes 
occurs. Accordingly we may find the corpuscles increased, normal, 
or diminished in different cases or at different times with the same 
case. 

Grawitz counted 4,900,000 red cells in a patient in comparatively 
good health, and three weeks later, when the patient had just been 
seized with the fatal coma, the count showed 6,400,000 per cubic 
millimetre. 

The white cells show no constant changes, except that v. Lim- 
beck has noted in several cases that the digestion-leucocytosis is 
unusually large even without previous fasting. Von Jaksch found 
leucocytosis in one of his eight cases, but on this point as on many 
others his results are almost unique. The only similar observation 
is that of Habershon,^ who reports moderate leucocytosis, decreased 
by strict diet. In thirteen cases I have never seen leucocytosis. 
One case of diabetic coma showed 4,200 leucocytes per cubic milli- 
metre. Another in a child of eight years showed 49,000 white 
cells. 

» St. Bartholomew Hosp. Report, 1890, p. 153. 



MYXCEDEMA. 



351 



GOUT. 

A few cubic centimetres of serum from gouty blood made acid 
with acetic acid (six drops of a twenty-eight-per-cent solution to 
every drachm of serum) deposit crystals of uric acid on a thread in 
from eighteen to forty-eight hours; but this is not always to be 
found, and is by no means peculiar to gout.' Uric acid is to be 
found in the blood in pneumonia, cirrhotic liver, nephritis, grave 
ansemia, leukaemia, and gravel ; also in health and after a meal of 
calf's thymus or any food containing much nuclein. 

The red corpuscles show no special changes except in severe 
chronic cases, which are sometimes anaemic. The white cells are 
increased according to Neusser, while v. Limbeck and Grawitz 
found the blood wholly normal. 

It is particularly in this disease that Neusser supposed the " peri- 
nuclear basophilic granulations " to exist in the white cells, which 
condition he believes to be characteristic of any " uric-acid diathe- 
sis." Futcher has conclusively disproved this. Fibrin is increased 
in acute cases. 

Ewing states that he found "uniform but moderate anaemia in a 
series of chronic cases examined at Eoosevelt Hospital, the patients 
all coming from the poorer classes. In the chronic cases leucocy- 
tosis of moderate grade may be observed, but it is difficult to 
determine its relation to the gouty process, as many of these 
patients suffer from other complaints." 

MYXCEDEMA. 

Le Breton^ examined the blood in one case both before and 
after thyroid treatment, and found that after forty days' treatment 
the red cells had risen from 1,750,000 to 2,450,000, the white 
cells , from 4,500 to 9,600, and the haemoglobin from 65 to 68 per 
cent. 

The remarkably high color index in this case before treatment 
(nearly 2. !) corresponds with the observations of Le Breton in the 
dried specimen, which ^owed a decided increase in the size of the 

1 It is important to evaporate the serum at a temperature not above 70° F., 
otherwise crystals will not form. 

2Le Breton: Ref. in Wien. med. Blatter, 1895, p. 49. 



352 



SPECIAL PATHOLOGY OF THE BLOOD. 



red corpuscles. He also noticed before instituting the thyroid treat- 
ment the presence of nucleated red cells and an excess of the poly- 
morphonuclear form of leucocytes. Under treatment tile nucleated 
red cells disappeared and the lymphocytes rose to their normal per 
cent. 

Putnam' has watched a similar case in which the number of 
red cells rose from 3,120,000 to 5,700,000 under thyroid treat- 
ment. 

Murray^ has collected 23 cases with blood examinations. Of 
these cases, 7 showed a normal blood count, 10 were ansemic, 4 
showed leucocytosis, and 2 exhibited both ansemia and leuco- 
cytosis. 

Kraepelin^ noticed (like Le Breton) a marked increase in the 
average diameter of the corpuscles in three cases, even when the 
count and the haemoglobin were normal. 

I have had an opportunity to examine the blood in four cases 
of this disease, but did not find anything remarkable in any one of 
them. 



Case. 


Red cells. 


White cells. 


Per cent 
Haemoglobin. 


Remarks. 


1 
2 
3 
4 


4,670,000 
4,460,000 
4,856,000 
4,012,000 


6,000 
8,800 
5,200 
7,900 


87 ■ 

80 
45 


Count 400 cells: Polynu- 
clear, 66^ ; lymphocytes, 
31.5^; eosinophiles, 2.5^; 
slight deformity of reds; 1 
normoblast. 



Differential counts were made in three cases, and no increase in 
the size of the corpuscles, such as Le Breton and Kraepelin saw, 
was present in these cases. The count showed : 



Case. 


Polymorphonuclear 
cells. 


Lymphocytes. 


Eosinophiles. 


1 




67 


28 


5 


2 




67 


27.8 


4.4 


3 




74 


26 





1 Putnam: Pel in Murray's article in "Twentieth Century Practice of 
Medicine," vol. iv. 

2 Murray: "Twentieth Century Practice of Medicine," vol. iv., p. 710. 
3 Kraepelin: Deut. Arch. f. klin. Med., vol. xlix., p. 587. 



graves' disease. 



353 



The increase of eosinopliiles in two of these cases may perhaps 
be due to the skin troubles in the disease. 

J. J. Thomas found a few myelocjrtes in a case of Putnam's. 

CKETimSM. 

Koplik^ records the following in two cases of sporadic cretinism : 
Case I. — Fifteen months old; advanced stage of disease. Hae- 
moglobin, 18 per cent. 

Case II.— Red cells, 3,026,000; Avhite cells, 13,500; haemoglo- 
bin, 105 per cent. This high haemoglobin corresponds to normal 
foetal blood. The child was nine weeks old, but its backward de- 
velopment is mirrored in the blood. As the case improved under 
thyroids the haemoglobin came down. 

GRAVES' DISEASE (BASEDOW'S DISEASE ; EXOPHTHALMIC 

GOITRE) . 

The blood is normal, except for an occasional associated chlorosis 
and sometimes a marked lymphocytosis. In one case I found 51.3 
per cent of lymphocytes and 1 per cent of myelocjrtes in 1,000 leu- 
cocytes, the polymorphonuclear cells bemg only 48 per cent ; but in 
fourteen other cases I have never found this again. The same fact 
has been noticed by Neusser (cited in Klein, loc. cit.). 

Oppenheimer found the red cells and haemoglobm normal in 
two cases. Von Jaksch^ in one case " complicated with myxoede- 
ma" found 3,818,000 red and 8,000 white cells. 

The association of Graves' disease with chlorosis is illustrated 
by two cases from Zappert :* 



Case. 


Red cells. 


White cells. 


Per cent 
Haemoglobm. 


1 


2,858,000 
2,738,000 


3,800 
3,800 


32 
30 


2 .... 





The same writer found eosinophiles much increased (8.5 per 
cent) in one out of four cases. 

1 New York Medical Record, October 2d, 1897. 
2Deut. med. Woch., 1889, p. 861. 
3Zeit. f. kiln. Med., 1893, p. 187. 
4Zeit. f. kiln. Med., 1893, p. 266. 

23 



354 SPECIAL PATHOLOGY OF THE BLOOD. 



Massachusetts General Hospital Cases. 





Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
Hfemoglobin. 


Remarks. 


1 


44 


M. 


3,668,000 


2.800 


45 




2 


27 






7.300 


65 




3 


42 




4,920.000 


7.700 


60 




4 


33 




4.464.000 


9.800 


63 


Died. 


"5 


44 






12.500 


50 


January 13. 








4,584,000 


12.700 




January 31. 








16,000 


56 


February 13. 










15.000 




February 15. 



ADDISON'S DISEASE. 

Some, but not all, cases are accompanied by marked anaemia. 
]S'eiimann' observed a case in which, the symptoms came on acutely 
and the red cells sank to 1,120,000 per cubic millimetre. During 
the convalescence which followed, the cells ran up above normal, 
reaching 7,700,000. 

Tschii'koff " reports two cases in which the red cells were re- 
spectively 3,280,000 and 2,933,000 at the lowest, but whose ha?mo- 
globin was extraordinarily high, over 100 per cent in one case. This 
he found on spectroscopic examination to be due to a great increase of 
reduced haemoglobin in the corpuscles. Methaemoglobin was also 
noted. 

The white corpuscles showed no changes, quantitative or quali- 
tative, exce^^t that they contained black pigment granules. Three 
cases have been examined at the Massachusetts General Hospital. 
The first, a woman of thirty, showed 6,240,000 red cells with 
14,000 white, and 90 per cent of haemoglobin. The differential 
count of 900 leucocytes showed the following figures : Polymorpho- 
nuclear cells, 53.4 per cent ; lymphocytes, 41 per cent ; eosinophiles, 
4.5 per cent; myelocytes, .9 per cent. 

The eosinophiles were very large, some of them eosinophilic 
myelocytes. 

The second, a man of forty-two, was very anaemic and weak at 
entrance and showed: Eed cells, 2,196,000; white cells, 7,500; 
haemoglobin, 20 per cent. Differential count of 200 leucocytes 
showed: Polymorphonuclear cells, 65 per cent; lymphocytes, 31.5 

^Neumann: Deut. med. Woch., 1894. p. 105. 
-Zeit. f. khn. Med., 1891, vol. xix.. Suppl. Heft 37. 



OSTEOMALACIA. 



355 



per cent; eosinophiles, 3.5 per cent; 5 normoblasts; marked 
poikilocytosis. 

Under suprarenal extract his blood improved in a month, till his 
red cells numbered 4,700,000; Avhite cells, 9,000; haemoglobin, 65 
per cent. 

The third, a man of fifty-two, showed : October 20th — red cells, 
2,848,000; white cells, 4,800; haemoglobin, 45 per cent. Decem- 
ber 10th— red cells, 2,624,000; white cells, 7,100; haemoglobin, 
45 per cent. Differential count: Polynuclear, 74 per cent; small 
lymphocytes, 22 per cent; large lymphocytes, 4 per cent; gosino- 
philes, .4 per cent. Xo nucleated red cells. 

A fourth patient, kindly sent me by Dr. Eogers, of Dorchester, 
showed: Eed cells, 2,864,000; white cells, 2,000; hsemogiobin, 51 
per cent. Differential count of 300 cells showed : Polymorphonu- 
clear cells, 63.3 percent; lymphocytes, 33.3 per cent; eosinophiles, 
2.3 per cent; basophiles, .3 per cent. 

I have never seen melanin in the leucocytes as Tschirkoff did in 
his two cases. 

Addison's Disease. 



Age. 


Ked cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


34 


5,056,000 


5,000 


60 


Soon died. 


39 


5,460,000 


117,000 


80 


Autopsy. 


29 


4,804.000 


10,000 


68 


Poh^nuclear, 77.6^. 








Lymphocytes, 14.0 










Eosinophiles, 8.0 










Myelocytes, .4 




519,200 


10,400 


80 





OSTEOMALACIA. 

The blood has for a long time been supposed, on the authority 
of V. Jaksch {Zeit. f. Mm. Med., vol. xiii., page 360), to exhibit a 
diminished alkalinity, the bones being supposed to be eaten away 
by acids in the blood. Von Limbeck and many other observers 
have lately shown that the blood is normal in alkalescence. 

Corpuscles and haemoglobin are usually within normal limits 
quantitatively, but Neusser reports an increase of eosinophiles and 
the presence of myelocjrtes in the blood. 

Ritchie^ confirms Xeusser and found also the yoimg leucocytes 
more numerous than normal. 

lEdin. Med. Journal, June, 1896. 



356 SPECIAL PATHOLOGY OF THE BLOOD. 

Fehling,' Sternberg,' Clirobak' found no increase of eosinophiles. 

Eieder's case was normal in all respects: Red cells, 4,892,000; 
white cells, 5,600; eosinophiles, 3.6 per cent; polymorphonuclear 
cells, 61 per cent. 

Ewing says : " The usual condition of the blood in osteomalacia 
appears to be that of moderate secondary anaemia. The leucocytes 
have varied from subnormal to moderately increased numbers. The 
lymphocytes are usually very numerous, an excessive proportion 
(maximum 56 per cent) having been found by Tschistowitch. High 
normal proportions of eosins have been found by several observers, 
but not by others." 

RICKETS. 

1. Ansemia is always present in severe cases and often in mod- 
erate ones. This, together with the fact that many cases of rickets 
are associated with an enlargement of the spleen, has led to the use 
of the misleading term "splenic anaemia." . There is no form of 
anaemia found in rickets that may not be found in other conditions 
(Morse). 

Hock and Schlesinger found an average of 2,500,000 red cells in 
a considerable number of cases with and without enlarged spleen. 

Yon Jaksch describes a case in which the red cells sank from 
1,600,000 to 750,000 within three months, and Luzet saw a simi- 
larly rapid process, the cells falling from 2,110,000 to 1,596,000 
within three weeks. On the other hand, in Morse's admirable 
study of twenty well-marked cases the red cells averaged over 
4,500,000 and not a case fell below 3,500,000. 

2. The haemoglobin is always relatively low ; it averaged 63 per 
cent in Morse's cases, a color index of about .7. Felsenthal got 
similar results. 

White Corpuscles. 

It is often difficult to say whether or not the leucocytes are in- 
creased, owing to the occurrence of most cases in infants at an age 
when leucocytes are always higher than in adults — how much higher 
at any given age depends largely upon the degree of vigor and for- 
wardness of development of the individual child. 

In Morse's series, for example, the average age of the infants is 
twelve months. And for this age none of the counts in his series 
^ Cited by Ritchie {loc. cit.). 



RICKETS. 357 

seem to me necessarily abnormal. They are all under 16,000 ex- 
cept three, these three being 17,900, 18,800, and 22,000 respec- 
tively, the latter in a nine months' infant. Many of the counts 
seem to me subnormal for infancy (5,500, 7,200). Most observers 
find leucocytosis present in many cases, but not in all. 

Qualitative Changes. 
Red Cells. 

As in all anaemias of infants, the ''degenerative " and "regener- 
ative " changes are relatively common. 

Polychromatophilic forms and nucleated corpuscles are fre- 
quently to be found, the latter often in great numbers but with a 
majority of the normoblast type. 

White Cells. 

Lymphocytosis is said to be marked, but, as wit^ the question 
of leucocytosis, we are never quite sure whether the numbers are 
abnormal for that age, for lymphocytosis is the normal condition in 
infants' blood. 

When, however, as in a case mentioned by Rieder, we find 75 
lymphocytes in every 100 leucocytes, the child being four years old, 
we are surely dealing with a pathological condition. Another of 
his cases, a seven-months' child, rachitic, with 57 per cent of lymph- 
ocytes, seems to fall within normal limits. Not so with Morse's 
cases. The highest percentage of lymphocytes in his series was 69, 
in an infant of two months. I have similar counts in health at that 
age. The average of his twenty cases is 43 per cent, which is, if 
anything, rather low for that age. The same difficulty arises with 
regard to the reports of eosinophilia in rickets, since eosinophiles 
are always relatively numerous in infancy. Morse's highest figure 
was 7 per cent his average 3 per cent. Hock and Schlesinger found 
20 per cent in one subject, and Weiss 16 per cent in another. 
They were highest in cases with splenic tumor. In Eieder's four 
cases and in the three seen at the Massachusetts General Hospital, 
no eosinophilia was present. Myelocytes in small number (.5-. 2 
per cent) are not uncommon, and may be considerably more nu- 
merous. 



CHAPTER IX. 

BLOOD DESTRUCTION AND HEMORRHAGIC DIS- 
EASES. 

PURPURA HEMORRHAGICA. 

The blood is practically that of anaemia from hemorrhage (red 
cells and haemoglobin reduced, white cells increased, occasional nu- 
cleated red corpuscles or polychromatophilic forms). Agello' has 
found methsemoglobin in the blood, and hence concludes that the 
disease is a poisoning of the corpuscles by ptomains absorbed from 
the intestine. 

The blood plates are much diminished and may be entirely absent 
in the worst stages. 

Bacteria of various kinds have been reported in the disease, but 
negative results are also common, and their presence is probably not 
significant. 

The red cells may fall as low as 2,500,000, but are much oftener 
slightly or not at all diminished. In many mild cases there are no 
demonstrable blood changes. On the other hand. Osier mentions 
a case which sank to 1,800,000, and the loss of blood may give rise 
to a fatal anaemia of the microcyte type (see page 154). 

Bensaude^ has observed that in 16 cases characterized by large 
hemorrhages (2 = acute "infectious," 2 with tuberculosis, 2 chronic, 
10 = Werlhof's disease) the clot shows no retraction and no transu- 
dation of the serum. Cases with small hemorrhages (toxic, rheu- 
matic, cachectic, and nervous) do not show any such abnormal 
characteristics. Hence he concludes that at the outset of a case of 
purpura, observation of the clotting process may enable us to fore- 
tell whether or not the case is to be of a severe or of a mild ty^^e. 
He found the blood lesion above described to be greatest during the 
hemorrhagic crises, slowly disappearing between them. Hayem 
has confirmed these observations. He finds the fibrin network al- 
most invisible. Despite this and despite the absence of contraction 
iRiforma Med., Kapoh, 1894, p. 103. '^La Semaine Med., 1897. p. 21. 



HEMOPHILIA. 



359 



in the clot, the actual rate of clotting is normal. Hayem has seen 
similar failure of contraction when the blood plates are plenty. It 
occasionally occurs in symptomatic purpura (e.^., from phthisis). 

SCURVY. 

There are no characteristic blood changes known. When hem- 
orrhage is severe the red cells may sink very low, to 557,875 in a 
case of Bouchut's; Ouskow and Hayem saw counts of 3,500,000 
and 4,700,000. The usual qualitative changes of secondary anaemia 
are present in severe cases ; haemoglobin suffers as usual more than 
the count of red cells. 

Leucocytes may be increased, whether from hemorrhage or from 
some complicating inflammatory process. This was not so in the 
following case of my series: January 26th — reds, 3,120,000; 
whites, 3,600; haemoglobin, 40 per cent. January 29th — reds, 
3,600,000, haemoglobin, 55 per cent. Eight days later haemoglobin 
65 per cent. 

" The red cells vary in number and size according to the length 
and severity of the disease. On account of the frequency of inflam- 
matory complications and hemorrhages the leucocytes are usually 
increased, Uskow finding as high as 47,000. Litten, however, ob- 
served no leucocytosis, and the writer in two well-marked but un- 
complicated cases found no increase" (Ewing). 

Barlow's disease may lower the red cells as far as 976,000 — as 
in a case of Eeinert's — ^the haemoglobin being 17 per cent, and the 
white cells 12,000. This was the day before death. The blood 
plates are not diminished, and the clot retracts normally. 

HEMOPHILIA. 

The blood changes are practically those just described and show 
nothing characteristic of the disease. Coagulation is slower than 
normal and blood plates are sometimes very scanty. The white 
cells are sometimes persistently diminished, as in the following cases : 



I. 





Sept. nth. 


Sept. 14th. 


Sept. 17th. 


Sept. 20th. 


Sept. 23d. 


Sept. 24th. 




3,960,000 










3,800,000 




3,400 


3,400 


3,800 


3,900 


3,700 


3,300 




43 per cent. 








64 per cent. 


49 per cent. 



360 SPECIAL PATHOLOGY OF THE BLOOD. 



II. 



February 8th. 


February 28th. 




4,400,000 


3,600,000 






5,000 


5,000 


1 Daily n( 


)se-bleed. 


30 per cent. 


28 per cent. 







BLOOD DESTRUCTION (H^MOCYTOLYSIS) . 
I. Besides the slow destruction of corpuscles which takes place 
in any ordinary anaemia, we have a group of conditions under which 
a large number of red cells are suddenly destroyed in the circulation 
itself. This may take place by — 

1. Separation of the haemoglobin from the corpuscles so that it 
colors the serum. 

2. Actual breaking to pieces of the red cells without separation 
of the haemoglobin. 

If normal blood is drawn and left to stand, the serum which 
separates from the corpuscles is not red-tinged or but very slightly 
so, provided all shaking and jarring are avoided. A very slight 
reddish tinge may appear in the serum even with most careful tech- 
nique. In some conditions the haemoglobin, while not actually 
separated from the corpuscles within the vessels, is so loosely con- 
nected to them that a considerable quantity separates post mortem 
and colors the serum in spite of the avoidance of any jar. 

This condition is to be distinguished from true haemoglobinaemia, 
in which the serum is actually colored before leaving the vessels, 
although the two conditions really represent only different degrees 
of vulnerability of the red cells. 

We are surer of a diagnosis of haemoglobinaemia when we find 
bits of broken-down cells in the fresh blood and the additional evi- 
dence of haemoglobinuria or jaundice. 

1. Severe forms of malaria, yellow fever, typhus fever, severe 
forms of septicaemia, and rarely scarlet fever may cause haemoglo- 
binaemia. Also alcoholism with fever, nephritis, cirrhosis, grave 
icterus, quinine poisoning, and eclampsia (Hayem) . 

2. Paroxysmal hannorjlohhmm'ia, so-called, is a variety whose 
cause is unknown and which does not seem secondary to any other 
disease, unless a certain relationship to syphilis be established, and 
to malaria. The attacks are brought on by a great variety of causes 
(cold, muscular or mental strain, etc.). Some persons can always 
bring on an attack by putting the hand or foot into cold water. 



BLOOD DESTRUCTION (hJEMOCYTOLYSIS). 



361 



Blood Examinatio7i. 

Coagulation is very rapid, but' the clot soon dissolves again 
(Hayem). The fresh blood occasionally shows deformities in the 
corpuscles or bits of broken cells, and lack of rouleaux if examined 
during a paroxysm. As a rule the corpuscles of the peripheral blood 
look normal. Frazer has recently reported a case in which he ex- 
cited a paroxysm by a cold bath, and studied the blood with great 
care. 



Time. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Blood plates. 


10 A.M. Before bath .... 


4,075,000 


15,000 


50 


450,000 


11 :05 A.M. Twenty - five 








minutes after bath; 










urine pale. 


3,633.300 


21.800 


50 


696,000 


11:45 (urine dark) 


3,760,000 


21,300 


60 


525,000 




4,200,000 


21,500 


50 


4,250,000(1) 




3,800,000 


17,700 


50. 


1,600,000 




4,100,000 


18,700 


50 


500,000 



The enormous increase of " blood plates " is striking. It is diffi- 
cult to resist the conclusion that these blood plates were bits of 
broken red corpuscles. The serum was currant-jelly colored. The 
appearance of the corpuscles was quite normal. 

All that is known of the disease is expressed by saying that for 
some reason the red cells are abnormally sensitive, so that any one 
of a variety of slight disturbances is sufficient to separate their 
haemoglobin and set it loose in the plasma. 

3. Extensive burns have been reported to cause haemoglobinsemia 
with breaking up of the red cells, presumably through changes in the 
serum similar to those which make duodenal ulcer so common a se- 
quel to bad burns. 

4. Snake poison and scorpion poison may have similar effects. 
II. Another group of corpuscle destroyers is that which works 

by changing the hcemoglohin to methcenioglohin. The most impor- 
tant of these is — 

1. Chlorate of Potash. — This destroys the corpuscles and pro- 
duces haemoglobinaemia and the usual train of symptoms (jaundice, 
dark urine, etc.) due to this. 

Brandenburg' examined the blood of a woman who had taken 
1 Berliner klin. Wocli., 1895, No. 27. 



362 



SPECIAL PATHOLOGY OF THE BLOOD. 



two and one-half ounces of chlorate of potash in water the night 
before. The blood showed marked leucocytosis, broken and dis- 
torted red cells. In gross it was chocolate-colored and the serum 
after separation of the clot was brown. The red cells progressively 
decreased as follows : 



Red cells. White cells. 

First day 4,300,000 20,000 

Second day 2.500,000 

Fourth day 2,300,000 

Fifth day 2,100,000 

Sixth day 1,900,000 

Seventh day 1,600,000 15,000 (death). 



Jacob^ studied a similar case : Thirty hours after a dose of 25 gm. 
of KCIO3 the blood showed: Eed cells, 4,425,000; white cells, 
80,000 (stained specimen resembles leukaemia). Next day, red 
cells, 1,825,000 (broken and decolorized); white cells, 60,800. 
Fourth day, red cells, 2,225,000; white cells, 14,000. 

2. Ehrlich anS. Lindenthal ^ report the case of a patient who was 
poisoned with nitrobenzol. Ten hours after the blood was chocolate- 
colored and showed methsemoglobin bands. Under the microscope 
there were no changes till the third day, when poikilocytosis ap- 
peared. 





Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Nucleated 
red cells 
per cubic 
millimetre. 


Fifth day 

Seventh day 

Eleventh day : . . . . 

Fifteenth day 

Seventeenth day 

Nineteenth day 

" " death. 


2,275,000 
1,845,000 
1,600,000 

905,000 
1,102,000 

900,200 


Much increased. 


55 
50 
44 
40 


2,070 

7,900 
24,700(!) 
12,000 

1,300 
540 



The nucleated red cells were at first mostly normoblasts ; later 
mostly megaloblasts. Posselt ' and Boas* have published similar 
cases. 

3. Antipyrin and antifihrin in doses of from thirty to forty- 
five grains may cause great cyanosis and dangerous prostration 



'Berl. klin. Woch., 1897, No. 27. 
2Zeit. f. klin. Med., 1896, p. 427. 
3Wien. klin. Woch., 1897, No. 30. 
4Deut. med. Woch., 1897, No. 51. 



ILLUMINATING GAS POISONING. 



363 



through the transformation of the haemoglobin and methsemo- 
globin. In certain persons, even much smaller doses produce the 
same effect. 

4. Phenacetin poisoning (K.voi\\g: Berl. klin. Woch., 1895) may 
cause actual blood destruction with anaemia in case the patient sur- 
vives the immediate effects of the deprivation of oxygen. A fatal 
case of chloral poisoning at the Massachusetts General Hospital 
showed 14,400 leucocytes with 54 per cent of haemoglobin. 

5. PliosphoTus 'poisoning (see Liver, page 311). 

6. Workers in aniline dyes and nitroglycerine factories may be 
severely poisoned by nitrohenzol compounds inhaled and producing 
methaemoglobinaemia. 

7. Pyrogallic acid and pyrogallol as used in treatment of skin 
diseases may lead to death through destruction of the red cells. 
Chromic acid (for instance, as applied through the vagina) may 
have a similar effect. 

Many other less common substances work the same ill effects on 
the blood. 

III. A third group of substances, of which carbonic oxide gas is 
the type, poison by combining chemically with the haemoglobin and 
preventing its combination with the oxygen of the air. 

1. IllumAnating gas is for our purposes the most im]3ortant of 
this group. 

The appearance of individual blood cells is not altered nor do 
they break up, but the corpuscles are useless to breathe with, as 
they cannot take up oxygen. 

The color of the blood is very bright red, much brighter than 
normal. 

Ped Cells. 

Von Limbeck' found in two cases 6,630,000 and 5,700,000 re- 
spectively. The volume of these corpuscles (estimated by Bleibtreu' s 
method) was greatly increased, amounting to .70.7 per cent (normal, 
41-48 per cent), so that apparently the size of the individual cells 
is increased. 

Mlinzer and Palma^ found 5,700,000 red cells in one case. 
Ehrlich found numerous normoblasts in one case. 

^ Log. cit., p. 234. 

3 2eit. f. Heilk., vol. xv., p. 1. 



364 



SPECIAL PATHOLOGY OF THE BLOOD. 



Leucocytes. 

Eaton' reported four cases, in all of which the white" cells were 
increased, the counts ranging between 15,000 and 22,000 per cubic 
millimetre. 

Miinzer and Palma {Joe. cit. ) found 13,300 in their case. Twenty- 
four such cases have been examined at the Massachusetts General 
Hospital with the following results : 



Table LIX. — Illuminating^ Gas Poisoning. 



Age. 


X* 

CO 


Red cells. 


Wuite 
cells. 


Per cent 

hfemo- 

globln. 


Remarks. 


41 


M 








uoni9. ; recovery. 




M 
IVl. 




til i , lUU 




September 12tli; corns,. 








1Q QOO 




September 13tli, entirely well. 


91 


M 
iVl, 




9R noo 


70 


Com9, ; recovery. 


1 Q 


M 
iVi. 




91^ A70 


Q7 


50 






25,200 






40 


M. 




22,900 


75 










21^200 




November 27tli; coma. 








15,500 




November 29th ; convalescent. 


Adult. 






22,000 




Recovery. 


60 


M. 




20,400 


75 


Coma; recovery. 


25 


M. 




20,360 


110 


Death. 


45 


M. 




20,100 




Coma; death. 


Adult. 






20,000 






64 






19,600 


80 




24 






18,800 






16 


F." 




18,500 


84 


Coma; recovery. 


27 






18,100 




50 






17,300 


90 


Temperature, 101°; recovery. 


22 






17,100 






19 


M. 




17,000 




December 22d. 








17,500 




December 23d. 






4,930,000 


17,000 






56 






15,600 






21 






15,000 


80 




55 






12,000 


60 




28 






9,400 






33 






9,300 


73 




20 






6,700 


58 





Warthen** reports the same condition in a single case. Here 
the specific gravity was also very high (v. Limbeck finds that this 
is to be explained by the increase in the actual size of the cor- 
puscles) . 

' Boston Medical and Surgical Journal, March 14th, 1895. 
2 Virchow's Archiv, vol. cxxxvi. 



PTOMAiN POISONING. 



365 



When there is any doubt as to diagnosis, the following test will 
settle it : Shake a small quantity of fresh-drawn blood into three 
times its volume of subacetate of lead. If the blood contains CO 
the mixture becomes of a line red color ; otherwise it turns choco- 
late-colored/ 

2. Da Costa (^Med. News, March 2, 1895) reported a considerable 
diminution in haemoglobins of patients during etherization, especially 
ansemic patients, but the investigations of Lerber^ do not confirm 
this. 

Tansy Poison big. — A single case examined at the Massachusetts 
General Hospital showed: Eed cells, 4,600,000; white cells, 21,- 
000; hsemogiobin, 70 per cent. 

Corrosive Poisoning (Ammonia Fumes). — A patient whose throat 
was covered with a fibrinous pseudo-membrane in consequence of 
inhaling ammonia fumes showed a leucocytosis of 25,800. Eed 
cells and haemoglobin normal. Another with vomiting and purging 
gave a count of 20,700 white cells. 



Ammonia. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


34 






37,000 




Mouth and pneumonia. 









Opium Poisoning (Chronic). — The majority of cases of the mor- 
phine habit show normal blood, but in October, 1897, a man of 
twenty-six entered the Massachusetts General Hospital for the mor- 
phine habit who showed at entrance 36,000 leucocytes per cubic 
millimetre. Five days later the count was 21,200. A differential 
count of 500 leucocytes made on this day showed : Polymorpho- 
nuclear neutrophiles, 71 per cent; small lymphocytes, 12; large 
lymphocytes, 10; eosinophiles, 6; myelocytes, 1. At the time 
of leaving the hospital he still showed a leucocytosis of 16,400. 
He had no fever, and the physical examination was entirely nega- 
tive. 

Ptomain Poisoning (Eotten Fish). — A mother and her four chil- 
dren were brought to the Massachusetts General Hospital suffering 

'Rubner: Zeit. f. anal. Chemie, xxx., p. 113. 
3 Inaug. Dissert., Basel, 1896 (see p. 109). 



366 



SPECIAL PATHOLOGY OF THE BLOOD. 



from the effects of decayed tish eaten that day. The blood showed 
the following: (1) mother: lencocytes, 21,600, of which 95.3 per 
cent were polymorphonuclear; (2) boy of seven years : leucocytes, 
19,900; (3) boy of three years: leucocjrtes, 56,800, of which 92 per 
cent were polymorphonuclear; (4) girl of five years: leucocytes, 
32,600; (5) girl of thirteen months: leucocytes, 55,400. The red 
cells and haemoglobin were normal. All the patients made prompt 
recoveries. 

Corrosive Poisoning. 
Carbolic Acid. 



Age. 


bex. 


Red cells. 


White cells. 


Per cent 
h£emoglobin. 


Remarks. 


27 
23 






10,300 
15,200 




Ko signs. 









Arsenic. 



66 



11,600 



ACUTE ALCOHOLISM. 

It has been shown experimentally that in animals made drunk 
with alcohol, there is an invasion of the blood and tissues by micro- 
organisms from the intestine. It may be that some of the counts 
here recorded are thus to be explained. 

Table LX. — Acute Alcoholism. 



Age, 



31 



27 
50 

35 
36 



Sex. 



38 M. 



Red cells. 



White cells. 



44.000 
32,000 
20,000 
42.000 
29,800 
25.000 
23,900 
15,900 



14,200 



Per cent 
haemo- 
globin. 



95 



Remarks. 



2d. 
3d. 

Followed by delirium tremens. 

Autopsy. 

Delirium tremens. 

Two M'eeks drinking hard; 

Temperature 102°; died- 

delirium tremens. 
TeniDerature 101°. 



PLUMBISM. 

Table LX. — Acute Alcoholism {Continued). 



367 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
hi^ino- 

^ILf UlLia 


Remarks. 


43 


M. 




12,000 


62 


Temperature 101^ ; delirium tre- 












mens. 


42 






12,600 




Clironic case delirium tremens. 


46 






11,000 












10.200 




Delirium tremens. 


32 


M. 


3, 936", 666 


10,200 


36(?) 




44 


M. 




9,600 


' 80 










8,100 






9Q 


X . 


'±,fCoO,\J\J\J 


o, uuu 


•55 


Delirium tremens. 


37 


M. 


7,800 


62 




60 


F. 




7.450 


65 










7,000 




December 21st. 








11,900 




December 26tli. 








6,800 












6,400 




Delirium tremens. 


32 


M. 




5,700 


68 


Autopsy. 


28 


M. 




5,600 




Delirium tremens. 








5,600 







PLUMBISM. 

Among the deleterious effects produced by lead in the human 
body, anaemia is one of the most serious. It is of the type of ordi- 
nary symptomatic anaemias except in one particular to which atten- 
tion has recently been called by Grawitz, viz., spotting or stippling 
of the red cells with fine basophilic granules, which can be well seen 
in specimens fixed in absolute alcohol for a few minutes and stained 
with Loefl&er blue, Goldhorn's polychrome, methylene blue, or other 
basic dyes. These basophilic granules are often seen in various 
forms of very severe anaemia, but in plumbism they appear eveii 
ivhen the ancemia is otherwise of a mild type. 

The following table exemplifies the degree of anaemia ordinarily 
seen : 



Table LXI. — Lead Poisoxing. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
h£emo- 
globin. 


Remarks. 


29 




4,500.000 


23,400 


50 


Lead colic and headache. 


30 




3,800.000 


22,800 


48 








16.800 




Eighth day. 


38 






22,700 


64 


31 




5,130,660 


14,800 


59 





368 SPECIAL PATHOLOGY OF THE BLOOD. 



Table LXL — Lead Poisoning {Contimied). 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 




40 






14,600 
11,400 




December 28tli. 








February 2d. 
Polynuclear, 71.2 per cent. 
Lymphocytes, 24.6 " 
Eosinophiles, 4.0 " 












Myelocytes, .2 " 


21 






12,600 
11,600 


72 


44 




3,888,000 


38 


Fits, colic, anaemia. 


35 




3,700,000 


10,U00 


50 


Colic. 


17 




3,820,000 


9,200 


48 


Chronic. 


33 




4,258.000 


8,600 


55 




32 




3,208,000 


7,200 


50 




52 




4,221,000 


7,100 


45 


August 10th. 
Polynuclear, 72.4 per cent. 
Lymphocytes, 23.3 " 
Eosinophiles, 2.5 " 
Myelocytes, 1.8 " 
Megaloblasts, 1. 
Normoblasts, 1. 






4,848,000 


O AAA 

8,00U 


KA 

00 


August JiOth. 
Polynuclear, 71.4 per cent. 
Lymphocytes, 25.6 " 
Eosinophiles, 2.6 " 
Myelocytes, .4 " 
Normoijlasts, 1. 


33 




4,000,000 


5,200 


50 




44 




3,056,000 


5,200 


45 




40 




4,500 















SUNSTROKE AND HEAT EXHAUSTION. 

The leucocyte count may be either high or normal, according to 
conditions not well understood. 

Sunstroke. 



Age. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Remarks. 


10 




24,000 


67 








13,400 




Two days later. 


35 




22,800 




Temp., 107°. Died. 


45 




21,000 




23 




10,000 




Temp., 110°, first day. 






5,200 




Temp., 104°, fourth day. Died. 


47 ■ 




10,000 


95 


50 




10,000 






32 




9,800 


62 





SUNSTROKE AND HEAT EXHAUSTION. 369 

Heat Exhaustion. 



Age. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Remarks. 






24,000 


80 


Recovery. 


62 




18,200 




Recovery. Temp., 98.8°. 






11,000 


75 


Recovery. 


34 




9,000 




Recovery. Temp., 98". 


54 




5,000 




Recovery. Temp., 99°. 



Age. 
25. 



24 



Electric Shock. 



White cells. 
8,900 



PART VI. 



MALIGNANT DISEASE, BLOOD PARASITES, 
AND INTESTINAL PARASITES. 



CHAPTER X. 

MALIGNANT DISEASE. 
The Blood as a Whole. 

1. The specific gravity is reduced in most cases, running roughly 
parallel with the haemoglobin. 

2. Coagulation is normal or slower than normal in uncomplicated 
cases. When sloughing and inflammation are present it may be 
rapid. 

3. Fibrin is usually normal ; an increase means inflammation in 
or around the tumor or an inflammatory complication. 

4. Occasionally the resistance of the red cells is extraordinarily 
low. In one of my cases the ordinary manipulations of preparing 
specimens (either fresh or film) for examination invariably mangled 
the red cells beyond recognition, no matter how quickly and care- 
fully the technique was carried out. In the fresh specimen the red 
cells seemed to fuse into each other in clumps, their biconcavity 
lost. The plasma became turbid with hsemoglobin despite every 
precaution. 

This was a case of cancer of the kidney with multiple haemor- 
rhage from various surfaces. I have never seen another case like 
this one, but in literature several such are mentioned. 

CANCER. 

Red Corjmscles. 

As in tuberculosis, we are frequently surprised to find but little 
diminution in the number of red cells. In all but very advanced 



CANCER. 



371 



cases this is the rule. It is a change of the individual red cells (pal- 
lor, loss of size, of weight, degenerative changes), rather than a re- 
duction of numbers. 

Nevertheless in the later cachetic stages of most cases of malig- 
nant disease, we do find a quantitative anaemia, the counts often 
running as low as 2,500,000 and occasionally sinking as low as in 
pernicious anaemia. Thus v. Limbeck records a case (complicated 
by repeated hemorrhages) with only 950,000 red cells per cubic 
millimetre. The lowest of my own cases was 1,457,000 per cubic 
millimetre. 

There seems to be no considerable difference between cancer and 
sarcoma as regards their effect on the red cells. The following table 
summarizes our cases : 

Table LXII., A. — Gastric Cancer. 



Red cells. 

Between 1,000,000 and 2,000,000 6 cases. 

2,000,000 " 3,000,000 17 " 

3,000,000 " 4,000,000 37 " 

4,000,000 " 5,000,000 29 " 

5,000,000 " 6,000,000 21 " 

Over 6,000,000 4 " 

Average, 4,090,000+ 114 cases. 



Nucleated red cells present in 11 cases out of 114 examined. NormO' 
blasts always in majority. A few megaloblasts in 3 cases. 

Table LXII., B.— Gastric Cancer. 
Leucocytes per cubic milHmetre. 



Between 3,000 and 4,000 1 case. 

" 4,000 " 5,000 4 cases. 

5,000 " 6,000 17 " 

6,000 " 7,000 9 " 

7,000 " 8,000 8 " 

8,000 " 9,000 8 " 

9,000 " 10,000 9 " 

10,000 " 12,000 6 " 

12,000 « 15,000 4 " 

15,000 " 20,000 ....12 " 

20,000 " 30,000 5 " 

30,000 " 40,000 3 " 



Total, 167 counts in 86 cases. 

Average, 10,600 + 



372 



SPECIAL PATHOLOGY OF THE BLOOD. 



Fifty-six additional cases give the following counts : 



O.UUU 10 


A nnn 


i 




K nnn 


A 

4: 




a nnn 


r- 
i 


a AAA a 


I*" nnn 


14 


7,000 " 


8,000 = 


10 


8,000 " 


9,000 = 


10 


9,000 " 


10,000 - 


15 


10,000 " 


12,000 = 


21 


12,000 " 


15,000 = 


14 


15,000 " 


20,000 = 


14 


20,000 " 


30,000 = 


3 


30,000 


40,000 = 


2 



115 counts. 

As will be seen by consulting Table LXII., A, the count of 
red cells is sometimes above normal, doubtless due to concentration 
of the blood from some cause. Probably the same influence is at 
work in other cases, and many of those showing normal counts have 
really fewer red cells than they should. Such abnormally high 
counts are not rare, as the following examples show : 



Author. 


Case. 


Affection. 


Red cells. 


Per cent , 
heemoglobin. 


Osterspey ^ . . 
Osterspey .... 
Osterspey. . .. 

Neubert^ 

Neubert 

Reinert^ 


1 
2 
3 
1 
2 


Cancer of the liver and stomach 


5,040,000 
6,184,000 
8,280,000 
5,085,000 
4,918,000 
6,200,000 


80 
87 
48 
73 
70 
77 



I wish to lay some stress upon this point, because it has been 
stated by some recent writers (e.r/., Grawitz : "Pathologic des 
Blutes," Berlin, 1896) that the red cells are almost always dimin- 
ished in malignant disease. 

The high counts in cancer of the gullet are obviously to be ex- 
plained by the lack of liquid taken, the blood being greatly concen- 
trated as in any other form of starvation. 

That this increase is not invariably present (see Table LXIIL, 
page 384) is doubtless because some oesophageal tumors permit the 

1 Dissert., Berlin, 1892. - Inaug. Dissert., Dorpat, 1889. 

3"Zahlung d. Blutkorp.," Leipzig, 1891. 



CANCER. 



373 



ingestion of liquid in normal amounts and of a certain amount of 
solids. In gastric cancer high counts are usually due to concentra- 
tion of the blood produced by vomiting or to the lack of absorption 
of fluid accumulating in a dilated stomach with pyloric obstruction. 

The highest counts in the Massachusetts G-eneral Hospital series 
are in simple gastric cancer without any stenosis at either end of the 
organs, and the lowest count (1,632,000) was in a similar case just 
before death. Taking all the cases of cancer in this series together, 
the average of the seventy-jive cases at the time when treatment began 
ivas 4^1-^0^000 red cells per cubic millimetre. 

In Osier and McCrae's 59 cases the average red count was 3,712,- 
186 per cubic millimetre. Their counts ranged: 



Over 6,000,000 3 cases. 

5,000,000 to 6,000,000 7 " 

4,000,000 " 5,000,000 17 " 

3,000,000 " 4,000,000 16 " 

3,000,000 " 3,000,000 8 " 

1,000,000 " 2,000,000 8 " 



Hcemoglobin. 

Bierfreund,^ who has examined seventy-two cases with regard to 
their percentage of coloring matter, found that in relatively slow 
and long-standing cases it averaged 68.5 per cent, and in the worst 
cases 57.5 per cent. In cases of mammary cancer after operation 
the hsemoglobin is of course lower owing to hemorrhage, and Bier- 
freund noticed that as a rule the haemoglobin began to rise toward 
normal much later than after operations for non-malignant condi- 
tions — a week later on the average —and that it never reached the 
'point at which it ivas before the operation.^ 

The following table from Bierfreund is of interest as illustrating 
these points. Cases were examined before and after operation, and 
the examinations were continued daily after the operation until the 
haemoglobin began to rise again. This occurred very late as com- 
pared with other operations. 

^ Langenbeck's Arcliiv, vol. xli. 

This is all the more extraordinary because Bierfreund specially noted 
that even in patients who gained weight notably after the operation the haemo- 
globin did not rise so high as it had been before operation; he watched them 
for months after it. Apparently the actual presence of the tumors is not the 
only cause of the lack of corpuscle substance. 



374 



SPECIAL PATHOLOGY OF THE BLOOD. 



Diagnosis. 


Per cent 
hgemoglobin 
bcf Or© 
operation. 


Per cent 
haemoglobin 
after 
operation. 


Per cent 


Regeneration time. 


Malignant tumor without 
complication. 

Very large or rapidly grow- 
ing tumors. 

Tumors with "softening" or 
disturbances of function. 


bo.o 
56.6 
57.5 


56 
38.4 

39.7 


15.5 
18.2 
17.8 


23 days. 
27.8 days. 
27 days. 


Total, 72 cases. 


Av. , 60 


A v., 42.8 


17.2 


Av. , 25. 9 days. 



By "regeneration time" is meant the number of days elapsed 
after operation before the haemoglobin beffhis to rise. After oper- 
ations for other causes (non-malignant) the average regeneration 
time is fourteen to twenty days. 

It is very important that these results of Bierfreund's should be 
tested. In Mikulicz's surgical clinic at Breslau all patients have 
their haemoglobin tested regularly. Osier and McCrae in 52 cases 
of gastric cancer record an average of 49.9 per cent of haemoglobin 
— a color index of . 63. Their readings were : 



Cases. Cases. 



80 per cent or more 3 

70 to 80 7 

60 " 70 6 

50 " 60 5 



40 " 50 8 

30 " 40 14 

20 " 30 7 

Below 20 2 



Keinbach^ examined 16 cases and found the haemoglobin range 
between 18 to 70 per cent^ with an average of 50 per cent. 

Eieder's" cases average 53 per cent (sarcoma much lower — see 
below) . 

Laker^ noticed the low haemoglobin percentage in malignant 
tumors and thought it a help in excluding benign tumors or tuber- 
culosis, in which the haemoglobin is much less diminished. 

In the 87 cases of malignant tumors in which I have notes of the 
haemoglobm (see tables) the average is 58 per cent. Comparing this 
with the average count of red cells (4,140,000), we get a color in- 
dex of . 65, distinctly higher than the average of chlorotic cases, of 
which, however, the figures distinctly remind us. The highest cases 

^ Langenbeck's Archiv, 1893, p. 486. 

2 "Beitrage z. Kenntniss d. Leucocytosis," Leipzig, 1892 (Vogel). 
sWien. med. Woch., 1886, Kos. 18 and 19. 



CANCER. 



375 



of this series had 100 per cent and 90 per cent of haemoglobin re- 
spectively, and the lowest 20 per cent and 22 per cent ; in these last 
two cases the color indexes were .36 and .58 respectively, not exces- 
sively low. As pointed ont by Taylor (Joe. cit.), cases of malignant 
disease can be divided into three gronps with reference to their 
blood : 

1. Those with approximately normal blood. 

2. Those with a low heemoglobm bnt a nearly normal number 
of cells. 

3. Those with great diminution both in cells and coloring 
matter. 

Among our own cases at the Massachusetts General Hospital 
about one-half fall under the second group, one-quarter under the 
first, and one -quarter under the third. 

As the disease progresses, the red cells and haemoglobin steadily 
go down (excexDt in cancer of the gullet), and at the time of death 
1,000,000 cells per cubic millimetre is not rare. It is very rare to 
find the red cells reduced below 1,000,000, much rarer than in per- 
nicious anaemia. Improvement under treatment is rare in cancer, 
common in pernicious anaemia. This is important in diagnosis. 

The color index usually remains below 1. Compared to most 
other varieties of secondary anaemia (e.^/., those in tuberculosis or 
nephritis), a quantitative anaemia — that is, a loss of red cells as 
well as of haemoglobin — is relatively more frequent. In general 
the degree of anaemia is parallel to the amount of cachexia, ex- 
cept when hemorrhage increases it (as in tumors of the stomach or 
uterus). 

How far the anaemia may be due to actual destruction of cells by 
toxic (?) products of the tumors is doubtful. Grawitz found that 
the injection of extracts of cancerous tissues caused in rabbits a 
temporary dilution of the blood, so that the cells per cubic milli- 
metre were diminished, and it may be that this plays some part in 
the causation of the low blood counts. 

Qualitative Changes. 

(a) The average diameter of the red cells is often diminished either 
(as in chlorosis) by a diminution of the size of nearly every corpus- 
cle, or by a less general shrinkage, many cells being of normal size. 
The very large forms seen in pernicious anaemia are rare in the anae- 
mia of malignant disease, and never, I think, reach the size of the 



376 



SPECIAL PATHOLOGY OF THE BLOOD. 



giant forms seen in the former condition. Very small cells, on the 
other hand, are as common in advanced cases as in any other form 
of anaemia, except chlorosis. Deformities and degenerative changes 
are very common in well-marked cases, often as great as in perni- 
cious anaemia, though they may be slight or absent. 

According to Strauer, the dcforinit'ies found in malignant dis- 
ease are greater than those found in any form of tuberculosis, and 
this fact he thinks of value in diagnosis. This observation has been 
confirmed by Taylor. 

Degenerative changes are sometimes Tvell marked, but seldom, if 
ever, reach so extreme a condition as occurs in many cases of per- 
nicious anaemia. 

(h) Xucleated red corjjuseles are the rule in all advanced cases, 
and in some others. Taylor found them in one-half of the twenty- 
two cases examined by him. Malignant disease differs in this re- 
spect from tuberculosis and most other conditions invohfing secondary 
anaemia, in that the nucleated red cells are much more common in 
cancer and may appear even when there is no considerable loss of 
red cells (numerically) or even when the haemoglobin is also normal 
(Schreiber). I have foimd them in four-fifths of all severe cases 
examined: 

As a rule the nucleated corpuscles are of the normoblast types 
(including small forms with dividing nuclei), but in very cachectic 
cases we may find megaloblasts as well — always, so far as I know, 
fewer in number than the normoblasts. Osier and McCrae found 
no typical megaloblasts in their 59 cases. The megaloblasts, when 
present, are in the minority as compared with the normoblasts. For 
example : 

C^^e I- ) ?tee''me^"sts. [ ^-^^n while counting 400 leucocytes. 
Ca- n. 3 Two novm^^^^^^ | Seen .hile counting 500 cells. 

Case III. ^^megrXsts" \ -'^^^ --ting 200 cells. 
Cases could easily be multiplied. 

The characteristics of the blood changes in malignant disease, 
then, so far as concerns the red cells, are those of secondary anae- 
mia, which at times attains the severest type — but only when 
cachexia is marked, or when hemorrhage complicates the disease. 

The specific gravity follows in a general way the haemoglobin 
percentage. 



CANCER. 



377 



On the white corjjuscles in malignant disease a great deal of in- 
terest has centred, and very conflicting reports have been published. 
As the effects of cancer and sarcoma seem to be somewhat different, 
we will consider them separately. 

1. The Leucocytes ix Caxcer. 

(rt) Quantitative Changes. 

We should expect great differences in the blood of different cases 
if we consider what a wide range is included between the small, 
hard, slow-growing, curable cancer of the lip which may produce 
little or no impairment of the general health, and the "fulminat- 
mg," rapidly growing cases with numerous metastases and profound 
prostration. 

The former class of cases may show a blood normal in all re- 
spects, including a normal leucocyte count ; while in the latter the 
blood may be so profoundly altered as to be confused with that of 
pernicious anaemia on the one hand, or with that of leukaemia on 
the other. 

In a general way it may be said that the more "malignant " the 
cases the greater the changes in the blood. 

The effect upon the leucocytes depends upon the following con- 
ditions : 

1. The position of the tumor. 

2. Its size, rapidity of growth, and the number, size, and posi- 
tion of its metastases. 

3. The resisting power of the individual. 

1. Position. — («) Tumors of the gullet invohTLQg stricture but 
not extending to other tissues are often accompanied by a diminu- 
tion of the leucocyte count, owing to the starvation which they pro- 
duce. This is not true of all cases, as is shown in the accompany- 
ing tables, but when the leucocytes are increased there is usually an 
involvement of other organs as well. 

(b) Cancers of the uterus and some of those of the stomach, by 
reason of the hemorrhage which they produce, are apt to be asso- 
ciated with a very high leucocvi;e count. 

(c) Tumors of the thyroid and of the pancreas are said by some 
writers to cause a specially great leucocytosis. In my own experi- 
ence, tumors of the kidney have shown very marked increase of 
white cells. 



378 



SPECIAL PATHOLOGY OF THE BLOOD. 



2. Size. — Other things being equal, the larger and more rapidly- 
growing tumors show in most cases a greater leucocytosis than small, 
slow-growing ones. 

Thus the cancers of the lip and of the pylorus, scirrhus of the 
breast or of the penis, show smaller counts than tumors of the liver, 
omentum, and kidney, which are apt to grow more rapidly. Metas- 
tases in the bone marrow are thought by some observers to give 
peculiar qualitative blood changes (see below). 

In general, metastases, being a method of rapid growth, simply 
add to the leucocyte count. 

These distinctions eliminate some of the apparent contradictions 
between the findings of different individuals who were simply de- 
scribing cancers of different types. But even within a single type, 
there are very marked differences in different cases. For instance, 
Alexander^ found the leucocyte count in cases of scirrhus of the 
breast to vary between 2,360 and 21,700. Similar differences have 
been reported in cancers of the stomach {e.g., Schneider^ finding 
leucocytosis in all of twelve cases, while Osterspey^ in another series 
of twelve cases found leucocytosis in only two). 

3. Reshting Fotver. — Possibly a part of these differences is to 
be explained by differences in the resisting power of the individual. 
But if this is so, we cannot measure the endurance of a given patient 
by his general health. As in the Civil War the pale, city -bred men 
outlasted the healthy farmers, so here the tumor's rapidity of growth 
seems often to be greatest in the most vigorous young individuals, 
while dried-up old women will resist its advance for a longer period. 

We come now to the conditions to be found in particular types of 
cancerous growth. 

Surprisingly little work has been done on the blood in malignant 
disease, such cases usually being under the charge of surgeons who 
rarely value such investigations. Except for scattered counts Jiere 
and there, all our knowledge of the corpuscles rests on the work of 
Hayem and Alexander in France, and Eieder, v. Limbeck, Pee, 
Sadler, Beinbach, Osterspey, Grawitz, Strauer, Schneyer, and 
Schneider in Germany. 

1 Alexander: ThSse de Paris, 1887. 
«Inaug. Dissert., Berlin, 1888. 
^ijiaug. Dissert., Berlin, 1892. 



CANCER OF THE BREAST. 



379 



CANCER OF THE BREAST. 

Most of our data come from Hayem' and his pupil Alexander.^ 

1. Scirrhiis Growths. — Number of cases, 14. Average leuco- 
cyte count, 11,400. Highest count, 21,700; lowest, 2,360— the 
last is somewhat doubtful as to diagnosis; except for this case, 
which was in a very old, dried-up woman, the lowest count was 
7,400. 

In 10 out of the 14 cases, the count was over 10,000. In the 3 
cases seen by the writer 2 showed no leucocytosis, 1 a considerable 
leucocytosis. 

2. Medullary {Encephaloid) Growths. — Three cases, all over 
10,000— average 11,300. 

Effects of Operation. 

The following figures from Hayem are also of interest: 
Case I. — Scirrhus of the Breast. 

Before operation 21,700 

Five weeks after operation (wound not quite 

healed) 10,000 

Wound completely healed 6,200 

Seven months after operation 8,990 (beginning to rise again) 

The growth recurred some months later and leucocytosis was again present. 

Case II. — Scirrhus of the Breast. 

First Second 

count. count. 

Before operation 11,500 11,450 

After operation 8,500 6,200 

Case III. — Scirrhus of the Breast. 

First Second 

count. count. 

Before operation 11,000 12,400 

After operation 8,400 

Case IV. — Scirrhus of the Breast. 

Before operation 7,400 

After operation 1,300 

Case V. — Medullary Cancer of the Breast. 

Before operation 10,000 

After operation 9,000 

Hayem considers that by watching the leucocyte count we can 
» Hayem: "Du Sang," Paris, 1889, p. 947. 

^G. Alexander: "De la Leucocytosis dans les Cancers," Paris Thesis, 1887. 



380 



SPECIAL PATHOLOGY OF THE BLOOD. 



predict the coining of a recurrence before any physical sign's are 
present. This he did in Case I. of the series just given. 

I have seen no confirmation or refutation of this statement. It 
is one of the many points to which the attention of surgeons should 
be directed. 

CANCER OF THE STOMACH. 

Here we have a much larger body of data to judge from. Thus : 
Hayem' in 12 cases found leucocytosis present in o, absent in 7. 
Schneider- in 12 cases found leucocytosis in 12 (all). 
Schneyer^ in 18 cases found leucocytosis in 4, and these 4 all 
under 11,000. 

Osterspey' in 12 cases found leucocytosis in 5. 
Rieder^ in 6 cases found leucocytosis m 3. 

Sadler^ in 13 cases fomid leucocytosis in 2, and in both there 
were complications (abscess of liver, perforation of gullet with gan- 
grene) to which the leucocytosis might be due. 

Reinbach ^ in 4 cases found leucocytosis in 2. 

Re inert ' in 2 cases found leucocytosis in 2. 

Laache' in 5 cases found leucocytosis in none.^ 

Despite these facts we have the record of a certain number of 
single cases in which the leucocytosis has been enormous. For in- 
stance, AYelch in Pepper's System of Medicine " mentioned a case 
in which the ratio of white to red cells was 1 : 25 (normally 1 : 750 ± ). 
Eisenlohr's'" case showed 1 white to 50 red, and Potain's" case 
showed 1 white to 48 red cells. 

The Massachusetts General Hospital series of 86 cases showed 
leucocytosis in 30 cases and none in 56 (see Table LXIL, B). Out 
of those showing leucocytosis 60 were under 12,500, that is, the 
leucoc3rtes were but slightly increased, leaving only 20 out of 86 (or 
twenty-three per cent) in which the leucocytosis was very marked. 

i"Du Sang," Paris, 1889, p. 948. Inaug. Dissert., Berlin, 1888. 

^luaug. Dissert., Berlin, 1892. ^ Loc. cit. 

5 Origiual-Mittlieilungen aus der Klinik v. Jaksch," 1891. 

" Langenbeck's Archiv, 1893, p. 486. Loc. cit. 

*"Die Anamie," Christiania, 1883. 

''Apparently, since he draws attention to the fact that there is leucocytosis 
in a case of cancer of the uterus. 

i^Deut. Arch. f. klin. Med., 1877, vol. xx. 
^iGaz. des Hop., 1888, No. 57. 



CANCER OF THE STOMACH. 381 

Among these 20, the highest counts were 40,000 and 39,000, and 
the highest ratio 1:62. 

In this series I have excluded all cases in which there was evi- 
dence of metastasis in other organs ; this means excluding 7 cases, 
6 of which showed leucocytosis, and helps to account for the low 
average leucocyte count in the other 86 cases. 

In over three-fourths, of these cases the diagnosis was made cer- 
tain either by operation or by autopsy ; all the others showed either 
a palpable tumor in old cachectic patients with pain and vomiting, 
or other equally clear evidence for the diagnosis. Doubtful cases 
have been excluded. As will be seen by the table, in some of the 
cases the counts were verified by repeated examinations, while in 
others only a single count — that made when the patient entered the 
hospital — was recorded. 

As a rule, the high leucocyte counts were in the more cachectic 
cases; but this does not always hold. Three cases in Table LXII., 
A, were very cachectic but showed no leucocytosis. 

The position of the tumor in one or another part of the stomach 
seemed to have no connection with the number of leucocyte^ Osier 
and McCrae found no leucocytosis in 29 cases out of 62, Their 
counts showed: 

Leucocytes. 



Below 5,000 14 cases. 

5,000 to 8,000 15 " 

8,000 " 12,000 15 " 

12,000 " 20,000 15 " 

20,000 30,000 3 " 



62 cases. 

Their highest count, 28,000, was in a case with extensive hepatic 
metastasis. The number seemed to bear no fixed relation to the situ- 
ation of the growth, nor to the amount of ulceration, of metastasis, 
or of fever. - 

On the whole, leucocytosis is relatively infrequent in cancer of 
the stomach, occurring in only about one-third of the early cases. 
As the disease progresses we may get a leucocytosis, particularly in 
case its growth is raxnd and metastases are frequent and numerous; 
but some cases, particularly those in which the tumor is small and 
grows slowly, may run their entire course without any leucoc}i:osis 
being present. In this respect they are like the majority of small, 
slow-growing cancers in other parts of the body (see below). 



382 



SPECIAL PATHOLOGY OF THE BLOOD. 



Hemorrhage or perforation is of course accompanied by an in- 
crease in the number of white cells — in fact the highest count in the 
present series (105,600) occurred in a case in which a cancer of the 
stomach with metastases in the liver perforated into the peritoneal 
cavity and started a virulent, quickly fatal peritonitis. 

DIGESTION LEUCOCYTOSIS IN CANCER OF THE STOMACH. 

A considerable body of statistics has accumulated to show that 
in the great majority of cases of gastric cancer the leucocji^osis of 
digestion (see above, page 98) does not occur. E. Miiller' noticed 
this fact in 5 cases of cancer of the stomach. Schneyer^ in 18 cases 
found it invariably absent, while in 3 cases of benign stenosis of the 
pylorus a considerable digestion leucocytosis appeared, as w^as also 
the case in 7 out of 8 cases of ulcer of the stomach, the exception 
being a fatal case. 

He found both incipient and advanced cases to be similarly af- 
fected. In 5 of his cases and in some of Mtiller's HCl was present 
in the gastric contents, so that the absence of digestion leucocytosis 
was not due to absence of HCl. 

Hartung^ in a series of 10 cases (mostly advanced) found no di- 
gestion leucocytosis, whereas a marked increase occurred in cases of 
malignant disease of other organs. Osier and McCrae found no 
digestion leucocytosis in 12 out of 22 cases. 

Capps" in 17 cases examined at the Massachusetts General Hos- 
pital found a digestion leucocytosis in 2, the increase being respec- 
tively 3,270 and 3,850 cells over the count before the beginning of 
digestion. In the other 15 cases there was no increase after a large 
proteid meal. Smce Dr. Capps' article 20 more cases have been 
investigated at the hospital, in 19 of which the digestion leucocy- 
tosis was absent. Thus in a total of 87 cases only S, or eight per 
cent, showed any digestion leucocytosis. In 5 out of 10 cases of 
chronic gastric catarrh the digestion leucocytosis was present ; it 
was also present in a case of benign stricture of the pylorus in a 
man of forty-nine on whom an operation was successfully performed 

^Prag. med. Woch., 1890, No. 17. 
2Zeit. f. khn. Med., 1895, p. 475. 
^Wiener klin. Wocli., p. 697, 1895. 
Boston Med. and Surg. Journal, November 4th, 1897. 



CANCER OF THE STOMACH WITH METASTASES. 383 



later. The digestion leucocytosis may, however, be absent in sim- 
ple debility. On the whole, it seems of little diagnostic value. 

Three cases of ulcer of the stomach showed marked increase, as 
did several cases of hyperacidity and other gastric disorders (see 
Diseases of the Stomach, page 300). 

CANCER OF THE STOMACH WITH METASTASES. 

Most writers have not separated the cases with metastasis from 
those without it. A glance at the 13 cases of Table LXIL, C, 
shows that with one exception leucocytosis was present throughout 
most of the disease. 



Table LXII,, C. — Cancer op the Stomach with Metastases. 



6 


Age. 


<D 


Red cells. 


White 
cells. 


Per cent 
bsemo- 
globin. 


Remarks. 


1 


54 




5,539,000 


3,900 a.c. 
4,200 p.c 


35 


Polynuclear, 65 per cent. 
Lymphocytes, 32 " 
EosinopMles, 3 " 


2 


48 


M. 


4,228.000 


5,000 

6,200 
7,300 


70 


January 23d. Stomach and 
liver. 

January 28th, mealtime. 
January 28th, three hours later. 


3 


66 


M. 




7,000 
14,400 
19,600 
21,640 


70 


Februarj^ 14th, no cachexia. 
March 6th, liver involved. 
March 12th. 
March 17th, cachectic. 




5,168,030 


62 


4 


56 






8,000 
8,500 a.c. 
7,600 p.c. 


85 


Operated. 


5 


45 




3,536,000 


8,100 


60 




6 


23 




3,120,000 


9,000 
19,000 


20 


Operation. 

Two weeks later. Died. 


7 


60 






15,000 
16,000 


60 


-f- Liver. 

Stomach, liver, and spleen. 


8 


Adult. 


M. 


3,352,000 


9 


44 




4,128,000 


17,100 


40 


-|- Liver. 


10 


54 


M. 


4,160,000 


24,000 


60 


Stomach and liver. 








24,200 
22,500 






11 


47 


M. 




34,350 

30,600 
105,600! 




November 7th, cancer of 

stomach and liver. 
November 11th. 
November 14th, perforation 






12 












peritonitis. 


41 


M. 


4,273,000 


10,000 


57 


Stomach, liver, and glands. 


13 


38 


M. 


5,432,000 


10,190 
13,653 


52 


January 6th. Stomach and 

liver. 
January 12th. 
January 22d, died. 



384 



SPECIAL PATHOLOGY OF THE BLOOD. 



CANCER OF THE GULLET. 

Most authors are agreed that 710 increase — in fact usually a de- 
crease — of white cells is the rule in this disease. Thus Eieder 
found 6,900 in one case; Ostcrspey's two cases showed no leucocy- 
tosis, and Escherich and Pee found similar resultSo^ This is prob- 
ably due to the fact that the position of the tumor, by causing star- 
vation, tends to lower the leucocytes, while it belongs to a class of 
small, slow-growing cancers which do not as a rule tend to produce 
leucocytosis. 

Nevertheless, ten of the eighteen cases in the Massachusetts 
General Hospital series (see Table LXIII.) did have leucocytosis, 
perhaps owing to some metastasis or complication. Three others 
showed a leucocytosis later. 

Table LXIII. — Cancer of the Gullet, 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


32 






5,400 






2 


50 






6,400 






3 


58 


M. 


3,488,000 


6,800 


100 


May 11th. 










6,800 




May 18th. 


4 


46 


F. 




7,000 




October 18th. 










10,600 














5,400 




October 19th, before food. 










6,600 




October 19th, after food. 










9,860 




October 20th. 


5 


62 




4,044,000 


7,000 


60 


December 29th. 








13,750 




January 31st. 










14,400 




February 25th. 


6 


67 






7,000 a. c. 














6,900 p. c. 






7 


51 


M. 


2,824,000 


7,600 


50 


Before food. 








11,500 




Four hours later. 


8 


56 


M. 


4,920,000 


8,725 


72 




9 


65 


M. 




11,100 


68 




10 


51 






10,300 






11 


65 






11,800 






13 


36 


ii. 




11,800 


30 


Haematuria also. 


13 


49 




6,624,000 


11,900 


90 


Vomiting 


14 


47 






13,700 


70 




15 


47 


M. 




15,400 


80 




16 


38 


M. 




15,600 


60 




17 


67 


M. 


4,604,000 


16,400 


60 


During digestion. 


18 


38 


F. 


4,560,000 


20,600 


50 





' Reinbach's two cases showed a diminution in the polymorphonuclear 
cells, which in all probability means a normal or diminished leucocyte count. 



CANCER OF THE LIVER. 



385 



CANCER OF THE LIVER. 
(See Table LXIV.) 

Out of forty-two cases, leucocytosis was present in twenty-five, 
others showing a leucocjrtosis later — a larger proportion than in 
gastric cancer. The cases were not all primary in the liver or bile 
ducts, but none originated in the stomach, and in all the greater part 
of the growth was in the liver itself. 

The comparatively great diminution in the red corpuscles will be 
noted in the Table XLIV. The condition both of red and white 
cells is doubtless due to the rapid growth of tumors of the liver as 
compared, e.g., with those of the stomach or lip (see below). 

Table LXIV.— Cancer of the Liver. 



Red 
cells. 



4,170,000 
3,834,000 

5,idd,()()b 

4,953,000 
3,784,000 
4,570,000 
4,573,000 



4,100,000 



4,073,000 



5,600,000 
3,800,000 



3,733,000 

4,108,000 
4.176,000 
3,856,000 

3,300,000 



4,160,000 



White cells, 



5,000 

5,300 

6,300 

6,800 

7,400 

7,800 
19,700 

8,000 

8,000 

8,300 

8,500 

9,000 

9,000 a.c. 
10,400 p.c. 

9,100 

9,100 a.c. 

8,500 p.c. 

9,300 



9,600 
13,500 

9,800 
33,000 

9,800 

30,000 a.c. 
18,800 p.c. 
9,970 
11,300 
10,300 
10,300 
10,400 
11,400 a.c. 
16,600 p.c. 
10,400 
10,800 
11,300 
13,650 a.c. 
14,750 p.c. 
11,150 
13,300 
13,000 
38,400 
13,600 
14,100 



Per cent 
haemo- 
globin. 



53 



63 



40 



60 



Remarks. 



Bile ducts = starting-point. Autopsy. 

Autopsy. 
Bile ducts. 

January 4th, 1896. Autopsy. 
February 12th, 1896. 
Operated. 



Gall bladder. 
Bile ducts. 



Difl., 1,000 cells: poly., 83.4 per cent; small 
lymph., 8.5; large lymph., 8.1; old lympho- 
cyte, 1. 

Gall bladder. 

November 6th i autopsy. 
December 5th. Poly., 75 per cent ; lymph., 23 ; 
eosinophiles, 3 ; reds, pale centres. 

December 31st. 
January 1st, 1896. 
January 3d, 1896. Autopsy. 



Poly., 68 per cent ; lymph., 30 ; eosinophiles, 3. 



Operated. 

Primary in bile ducts. Autopsy. 
April 36th. Bile ducts and gall stones. 
April 36th. 



January SOth. Jaundiced. 
January 38th. Died January SOth. 

July 17th. Autopsy, July 19th. 



25 



386 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table LXIV. — Cancer of the Liver {Continued). 



Age. 


X 

a; 


Red 
cells. 


White cells. 

■ 


Per cent 
haemo- 
globin. 


Remarks. 


56 




3,956,000 


14,200 


47 


Poly., 84 per cent ; lymph., 15.6 ; eosinophiles, 4. 








14,900 a.c. 




January 17th. Gall stones. 








17,800 p.c. 








5,120,000 


65 


January 24th. 


53 




4,400,000 


15.600 


75 


64 


M, 


2,768,000 


15,800 


45 


May 6th. 






2,880,000 


21,9f)0 




May 24th. 








1,530 


45 


May 28th. 






2,928,000 


11,700 




June 8th. 


30 


F. 


3,660,000 


17,200 


82 


Poly., 83 per cent ; myelocyte, 1. 








16,800 




48 


F. 


2,900,000 


17,500 


48 


Poly., 92 per cent ; lymph., 5.8 ; eosinophile, 1 ; 












myelocytes, 2. Autopsy. 


63 




3,864,000 


17,600 


55 




31 


M. 


3,130,000 


18,700 


52 


December 20th. 






15,600 




December 30th. Before food. 








14,000 




December 30th. Four hours later. 


37 






20,600 












19,000 a.c. 












20,000 p.c. 






66 




3,704,000 


21,000 


50 




58 




23,200 




January 31st. 








22,200 




February 12th. Abscess of liver. 


Adult 


M. 


4 408 000 


25 500 


70 


46 




2,824,000- 


32^600 


33 


Omental hernia. Purpura h^emorrhagica. In- 










ternal hemorrhage. Poly., 84.8 per cent; 












lymph., 15.2; eosinophiles, 0; no nucleated 












reds; considerable variation in size ; moderate 












poikilocytosis. 


50 


M. 


4.544,000 


35,600 




November 29th, 1895. 






36,400 




December 10th, 1895. 






3,136,000 


23,000 




January 15th, 1896. 






4,056,000 


28,000 




February 16th, 1896. Autopsy. 








.Tan. 


Feb. 





28,000 
26, 000 
24, 000 
20,000 
18,000 
16,000 
14,000 
12,000 
10,000 



24 




28 


30 


4 


5 


8 


9 


10 


11 


12 


13 


14 
















































































A 






























V 














































































































Di 


ed 0 


a 15 


til 































Fig. 35.— Chart of Leucocytes in a Case of Cancer of the Liver. 



CANCER OF THE INTESTINE. 
Here the counts range both high and low. 

Hayem^ found cancer of the rectum to show only 9,500 leuco- 
cytes. Reinbach ^ found in three cases of cancer of the rectum mod- 
1 Loc. cit. ^ Loc. cit. 



CANCER OF OMENTUM AND ABDOMINAL ORGANS. 387 



erate leucocytosis/ Only ten of the twenty -five cases in our series 
(see Table LXV.) showed leucocytosis, and in one of these there was 
a complicating pylephlebitis which probably raised the count. 
The red cells show little change. 



Table LXV. — Cancer of the Intestine. 













Per cent 








x' 


Red cells. 


White cells. 


haemo- 


Remarks. 


;z; 


< 


V 
OQ 






globin. 




— 
1 


56 


M. 




4,408,000 


12,700 


60 


Cancer of duodenal papilla with pylephlebitis. 














Autopsy. 


2 


41 


F. 


5,560,000 


5,800 


45 


Cancer of cfecum. Operated successfully. 


3 


31 


M. 


4,921,000 


8,800 




Cancer of hepatic flexure. Operated. 


4 


33 


M. 


4,368,000 


5,800 


83 


Cancer of colon. Operated. 


5 


59 


F. 


4,800,000 


.5,500 


33 


Cancer of caecum. Autopsy. 


6 


66 


M. 


4,268,000 


7,1.50 


78 


Cancer of intestine (where ?). 




50 


F. 


.5.416,000 


12,000 




Cancer of the rectum. 


8 


58 


M. 


4, iDU,UuU 


15,200 


50 


Cancer of rectum. Operation. 


9 


34 


M. 




15,-500 


40 


Metastases, primary in sigmoid. 


10 


52 


M. 




7,400 


55 


Metastases, primary in sigmoid. 


11 


47 


F. 




9,300 


63 


Cancer of csecum. 


12 


28 


M. 




5,300 


72 


Cancer of cEecum. Operation. 


13 


52 


M. 


2,424,000 


7,800 




Cancer of caecum. 








2,440,000 


6,800 




No digestion leucocytosis. 


14 


59 






6,000 


35 


December 7th. 








3,4.52,000 




40 


December 9th. Polynuclear, 65.6 per cent ; lym- 














phocytes, 31 ; eosinophiles, 3 ; basophiles, .4. 








3,840,000 


11,700 


40 


December 21st. 


15 


62 






6,400 a.c. 




Hepatic flexure. 










10,000 P.O. 




16 






3,504,000 


7,400 a.c. 


50 


Hepatic flexui-3. Polynuclear, 80 per cent ; lym- 










8,300 p.c. 




phocytes, 19 ; eosinophile, 1. 


17 


39 






7,.500 




18 


50 






7,800 






19 


36 




3,.504,000 


9,800 


40 


Operated. 


20 


34 




4,524,000 


10,800 


38 


Rectal. Polynuclear, 78 per cent.; lymphocytes. 


21 












19.8 ; eosinophiles, 2.2. 


45 




3,358,000 


11,500 


25 


Polynuclear, 68 per cent.; lymphocytes, 28.5; 


22 


17 










eosinophQes, 3.5. 






13,600 




23 


53 




5,960,000 


13,700 


60 




24 


46 






21,600 


80 


Rectal and omental. 


25 


62 






25,200 


75 





CAXCER OF OMENTUM AND ABDOMINAL ORGANS 
GENERALLY. 

The nineteen cases seen at the Massachusetts General Hospital 
in which cancerous tissue was pretty generally distributed through 
the abdominal organs, all showed leucocytosis with six exceptions- 
(see Table LXVL, A). 

^ Apparently — that is, the percentage of adult cells was increased. He did 
not count the leucocytes as a whole. 



388 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table LXVI., A. — Cancer of Omentum and Abdominal Organs 

Generally. 



Red cells. 



Wbite cells. 



Per cent 
haemo- 
globin. 



Remarks. 



5,440,000 
6,073,000 



3,453,000 
3,840,000 



4,560,000 



3,860,000 



3,772,000 
4.496,000 
2,995,000 

8,000,000 



5,500,000 



Greatly 
Increased. 



5,350 
5,800 
6,000 



Markedly 
diminished. 



26,200 
37,400 

Greatly 
Increased. 



40 



11,700 


40 


7,250 




6,5001 




7,300 (" 




7,800 


60 


10,600 




7,800 a.c. 




8,100 p.c. 




8,000 


65 


8,300 




9,000 




10,600 


35 


9,600 




11,700 




13,600 


68 


14,200 




13,700 




152,000 


45 


18,000 


60 


20,400 


50 


12,600 


65 



Markedly 
diminished. 



Primary in pancreas. Differential count of 
400 cells : Polynuclear, 84.5 per cent ; small 
lymphocytes, 8; large lymphocytes, 5; 
eosinophiles, 2.5. Autopsy. 

Colon. 



December 9th. Polynuclear, 65.6 percent; lym- 
phocytes, 31 ; eosinophiles, 3 ; basophiles, 4. 
December 21st. 
May 13th. 

May 20th. No digestion leucocytosis. 

October 13th. Polynuclear, 88 per cent ; lym- 
phocytes, 10 ; eosinophiles, 2. 
October 16th. 



Caecum. 

General in abdomen. 

Polynuclear, 84 per cent ; lymphocytes, 10.2 ; 
eosinophiles, 6; myelocytes, 8; normo- 
blast - 1. 

February 10th. 

February 18th. Peritoneal. Autopsy. 

Autopsy. 

Peritoneal. 

Polynuclear, 79; lymphocytes, 14.5; eosino- 
philes, 3.5. Kidney and spleen. 

Polynuclear, 88 per cent; lymphocytes, 10; 
eosinophiles, 2 ; normoblasts = 16 ; megalo- 
blasts = 2. Count 500 cells. Size reds all 
right. 

Autopsy, 

Questions of aneurism. Autopsy. 
Differential count of 500 cells. Polynuclear, 
80 per cent ; lymphocytes, 30. 



CANCER OF THE KIDNEY. 

Of ten cases which I have examined (see Table LXVI., B) eight 
showed large leucocy tecounts— viz., 12,900, 19,980, 25,000, 27,000, 
28,500, 43,100, 82,000, and 91,000. In three of these cases, how- 
ever, the tumors may have been sarcomata, as no microscopical ex- 
amination was made. Most of the cases had fever, chills, and signs 
of inflammation, which may account for part of the leucocytosis. 



Table LXVI., B.— Cancer (or Sarcoma) of Kidney, 



o 
.;2; 


a3 
< 


Sex. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


58 




3,840,000 


7,600 


50 






2 


48 






8,100 




Autopsy. 




3 


76 




5,046,000 


9,100 


45 


Sarcoma. 





CANCER OF THE UTERUS. 389 
Table LXVI., B.— Cancer (or Sarcoma) of Kidney {Continued). 













Per cent 




6 


be 


X 


Red cells. 


White cells. 


haemo- 


Remarks. 




CD 






globin. 












19,980 




Autopsy. 


4 


14 






ii,DUU a.c. 
i^^vyn) p.c. 

7,900 a.c. 

9,000 p.c. 




March l4th. Polynuclear, 72 per cent.; lympho- 
cytes, 27 ; eosinophile, 1. 
March 17th. 


5 








23,000 
25,000 




Autopsy. 

Differential count of 800 cells : Polynuclear, 80.9 


6 


53 


M. 


4,312,000 


32 










per cent.; lymphocytes, 15.8 ; eosinophjles, 3.3. 
No nucleated red cells. 


7 


2 


F, 


3,756,000 


27,000 




Differential count of 500 cells : Polynuclear, 66 








per cent.; lymphocytes, 29.5; eosinophiles, 2; 
myelocytes, 2.5 ; normoblasts, 24 ; megaloblasts, 
2. Autopsy. 


8 


57 


F. 


5,200,000 


28,500 




Supposed leuksemia. Differential count of 500 
cells: Polynuclear, 81.8 percent.; small lym- 














phocytes, 12 ; large lymphocytes, 4.2 ; eosino- 
philes, 2. Autopsy. 














9 


49 


F. 


3,360,000 


43,100 




Supposed leuksemia. Differential count of 1,000 










cells : Polynuclear, 92.9 per cent.; lymphocytes, 
6.2; myelocytes, .9; normoblasts, 3 ; megalo- 
blast, 1. Autopsy. 


10 


50 


F. 


4,111,000 
2,780,000 


82,000 
91,000 




July 8th. 

Polynuclear, 98 per cent.; lymphocytes, 3. 



Von Limbeck's' case mounted steadily from 18,514 to 80,541. 



CANCER OF THE UTERUS. 

In six cases Hayem^ found no increase— the counts ranging from 
4,575 to 9,500 with an average of 7,800. 

Rieder,^ on the other hand, in a single case found 30,800, and 
the seven cases counted at the Massachusetts General Hospital 
showed a leucocytosis in five (see Table LXVII., A). 

There is need of more data on this subject. 



Table LXVII., A.— Cancer of the Uterus. 



d 


Age. 


X 

a; 

OQ 


Red 
cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


35 






6,400 


62 
43 




2 


43 




4,772,000 


8,600 




3 


59 




16,800 




First day. 










7,400 a.c. 




Third day. " 










12,000 p.c. 




4 


48 


F. 


2,696,030 


19,400 


20 


October 26th. 








3,232,000 


30,700 


27 


October 28th. 


5 


51 


F. 




34,900 




Differential count of 1,000 cells : Poly., 88 per 














cent ; small lymphocytes, 11.7 ; eosino- 














philes, .2; myelocytes, .1. Two normoblasts. 


6 


31 


F. 


2,889,680 


22,250 




7 


28 


F. 




20,170 


75 


Ureter blocked ; anuria nine days. Autopsy. 



Loc. cit. Loc. cit. ^ Loc. cit. 



390 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table LXYIL, B. — Cakcer of the Ovary. 



o 
12; 


Age. 


Sex. 


Red 
cells. 


White 
cells. 


Per cent 
hEemo- 
globin. 


Remarks. 


1 


50 




3..532,000 


16,400 


50 




3 


36 


F. 


4,500,000 


35,000 


62 


Operation. 


3 




r. 


3,248,000 


32,800 




Operation. 










Cancer of the Prostate. 


1 


63 




2,596,000 


9,200 


35 


December 13th. 








2,212,0)0 


11,000 




December 19th. 














Polynuclear, 74.4 per cent; lymphocytes, 














23.6 ; eosinophiles, 2. 


3 


45 


M. 




10,200 




3 


51 






18,000 







11 51 1 M. ! 7,000,000 



Cancer of the Lip. 

6,300 I I 

Cancer of the Breast. 



1 


31 


F. 


6,000,000 


8,200 


2 


? 


F. 




Not 










increased. 


3 


? 


F, 




Marked 










increase. 


4 


57 




5,200,000 


12,200 


5 


60 




18,000 










14,000 



Differential count of 600 cells : Poly., 72.4 per 
per cent ; lymphocytes, 25.4 ; eosinophiles. 

Differential count of 400 cells : Poly., 89 per 
cent ; lymphocytes, 11. 

First day. 
Third day. 





43 1 M. 1 . . . . 








1 increase. | 



Cancer of the Neck. 

I Poly., 88.5 per cent. 



Cancer of the Pancreas. 



1 


55 


M.I 


1 18,300 


70 


Metastases. 


s 


56 


M. 


17.600 




Liver and spleen also. 


3 


64 


M. 1 


1 15,900 




General peritonitis. 



II 63 IF. 



II 59 I M. I 



Cancer of Vertebrae. 

. . I 13,200 1 . . I 

Adenoma of the Suprarenal Body. 
. . I 34,300 I . . I Autopsy. 

Mediastinum. 



3.5 






10,700 


70 


April 30th, Polynuclear, 87 per cent. 
April 26th. Lymphocytes, 13 " 








9,300 










8,300 




April 27th. Eosinophiles, 1 " 








6,800 




May 1st. 


47 




5,008,000 


13,800 


30 


July 7th. Stricture oesophagus. Larjux. 






14,000 




July 18th. No autopsy. 



Skull. 



9,300 
8,600 
15,800 
14,600 







14,600 I 


70 1 


1 63 .... 


4,76d,bbb 1 


5,000 


60 



Cerebral. 
May 7th. 
May 22d. 

May 38th. Metastases. 



General. 

Multiple myeloma. (Wright.) 



CANCER OF THE UTERUS. 



391 



Cancer of the lijj has apparently been neglected so far as blood 
examination is concerned. Hayem, Rieder, and Eeinbach give but 
one case each, the counts being respectively 7,000, 11,600, and "not 
increased." In a single case at the Massachusetts General Hospital 
I found 6,300. 

The following scattered counts may be added : Cancer of tongue, 
7,000 (Hayem) ; cancer of scrotum, 6,700 (Hayem) ; cancer of navel, 
7,100 (Hayem); cancer of larynx, 7,200 (Hayem), 16,000 (Eein- 
bach) ; cancer of ovary, 25,000 (Massachusetts General Hospital) 
and "no increase" (Eeinbach) ; cancer of neck, 20,000, Massachusetts 
General Hospital, and no increase (Eeinbach) ; cancer of pancreas : 
Hayem, 2 cases— 9,400 and 9,900; Schneider, 1 case— 12,000; 
cancer of vagina, 9,800 (Eieder) ; cancer of penis, 7,000 (Hayem) ; 
cancer of thyroid, 70,000 (Hayem) (a very rapidly growing tumor) ; 
cancer of mediastinum, " marked increase " (Eeinbach) ; cancer of 
prostate,^ 10,200. 

Qualitative Changes in the Leucocytes. 

1. The percentage of polymorphonuclear neutrophiles is usually 
high in cases with leucocytosis and normal in those without it. This 
rule holds for perhaps three-fourths of the cases, but there are many 
exceptions to it. For instance, Taylor^ reports 27,840 leucocytes 
with 65.6 per cent polymorphonuclear cells, 14,800 leucocytes with 
66.2 per cent polymorphonuclear cells, 25,000 leucocytes with 58.2 
per cent polymorphonuclear cells, 45,000 leucocjrtes with 43.7 per 
cent polymorphonuclear cells, the last a marked lymphocytosis. 
On the other hand, he found 88.7 per cent of polymorphonuclear 
cells in a total leucocyte count of 3,000. My own experience is 
similar — i.e., 88 per cent of polymorphonuclear cells with a total 
count of 7,800 leucocytes, though I have never seen so marked a 
lymphocytosis as was present in Taylor's cases. He also noted a 
relative increase in the large lymphocytes which my counts have not 
shown. Osier and McCrae found an average of 81 per cent of poly- 
morphonuclear cells in 22 cases, the higher percentages being in the 
cases with highest total leucocyte count. These writers confirm the 

^Braun (Wien. med. Woch., 1896, p. 582) mentions a cancer of the prostate 
in which the leucocytosis, instead of being made up mostly by the adult leuco- 
cytes, was associated with a large increase of the small lymphocytes together 
with numerous eosinophilic myelocytes. 

2 Taylor: Internat. Med. Mag., July, 1897. 



392 



SPECIAL PATHOLOGY OF THE BLOOD. 



observation of Taylor that the large mononuclear and transitional 
leucocytes are often relatively increased in cancerous disease. Tay- 
lor found in 15 cases with leucocytosis an average of 19.3 per cent 
of these cells and in 6 cases without leucocytosis 26 per cent. 
Eight of these cases were cancer of the stomach — the remainder 
cancer of other organs. All were cachectic. Osier and McCrae in 
22 cases of gastric cancer record an average of 8.5 per cent of large 
mononuclear and transitional varieties. They do not agree with 
Taylor in believing the excess of these cells is sufficient to be of 
diagnostic value. 

Eeinbach found in 8 cases with leucocytosis 89 per cent in 2 
cases and 87, 86, 83, 81, 80, and 77 per cent in others. In the 
Massachusetts General Hospital series the following percentages 
occurred: When no leucocytosis was present, 88.7, 88, 86, 79, 66, 
62.5, 62, 60, 57 per cent, etc. AYith leucocytosis, 96, 98, 92, 90, 
90, 88, 87, 86, 84, 83, 74 per cent, etc. (see Tables LXIL, LXIV., 
LXYL, LXYIL). 

2. Eosinojihiles are not always notably decreased (as they are in 
many other leucocjrtoses) nor are they increased except when bone 
metastasis occurs (see below). In Eembach's 16 cases the average 
percentage was 2 -|- per cent. In Osier's 22 cases it was 1.1 per 
cent. In the Massachusetts General Hospital cases the average 
was 1.2 per cent, but in 7 of the 38 cases in which differential counts 
were made, no eosinophiles were seen. 

3. Myelocytes. — Perhaps more commonly than in other conditions 
except leukaemia and pernicious ansemia, we find in malignant dis- 
ease small percentages of myelocytes, as the following cases show : 

Case I. — Extensive abdominal cancer ; great cachexia. Six hun- 
dred cells showed : 

Per cent. 

Poly nuclear neutrophiles 89.4 

Lymphocytes 10. 

Eosinophiles 1 

Myelocytes (3 in 600 cells) 5 

Case 11. — Cancer of uterus; marked cachexia and leucocytosis 
One thousand cells showed : 

Per cent. 

Polynuclear neutrophiles 82.3 

Lymphocytes 17.3 

Myelocytes (4 in 1,000 cells) 4 

Case III. — Cancer of uterus; died two days later. Red cor- 



CANCER OF THE UTERUS. 



393 



puscles, 7,000,000 ; white, 62,000. Considerable stasis helps to ex- 
plain the count. Differential count of 500 cells showed : 



Per cent. 

Polynuclear neutrophiles 93 

Lymphocytes 6 

Eosinophiles 0 

Myelocytes (5 out of 500) 1 

Case IV. — Cancer of liver, jaundice, and cachexia; died soon 
after. Differential count of 500 cells showed : 

Per cent. 

Polynuclear neutrophiles 92. 

Lymphocytes .... 6. 

Small myelocytes 1.2 

Large myelocytes (4 in 500) 8 

Case V. — Cancer of abdomen; cachectic. Differential count of 
1,000 cells showed: 

Per cent. 

Polynuclear neutrophiles 82. 

Lymphocytes 16.6 

Eosinophiles 1. 

Myelocytes (4 in 1,000) 4 



Case VI. — Cancer of stomach, liver, etc., with perforated stom- 
ach; cachexia. Leucocytes, 105,000. Fifteen hundred cells 



showed : 

Per cent. 

Polynuclear neutrophiles 90.7 

Lymphocj^tes 4.8 

Eosinophiles 2 

Myelocytes (68 in 1,500) 4.3 

Case VII. — Cancer of uterus; cachexia. In 1,000 cells there 
were : 

Per cent. 

Polynuclear neutrophiles 88. 

Lymphocytes 11.7 

Eosinophiles 2 

Mj^elocytes 1 

Case VIII. — Cancer of kidney; great cachexia. In 1,000 cells 
there were : 

Per cent. 

Polynuclear neutrophiles 92.9 

Lymphocytes 6.2 

Myelocytes 9 



394 



SPECIAL PATHOLOGY OF THE BLOOD. 



Case IX.- — Cancer of kidney; great cachexia. Leucocytes, 27,- 
000. Five hundred cells showed: 

Per cent. 

Polynuclear neutropliiles 66. 

Lymphocytes 29.5 

Eosinopliiles ... 2. 

Myelocytes 2.5 

Case X. — Cancer of liver. Five hundred cells showed: 

Per cent. 

Polynuclear neutropliiles 92. 

Lymphocytes 5.8 

Eosinophiles 2 

Myelocytes 2. 

About one-half of all the cases of cancer examined by me have 
shown myelocytes. 

Epstein' in a case of cancer with metastatic bone nodules noticed 
large numbers of nucleated corpuscles (normoblasts and megalo- 
blasts) and myelocytes, but I think the association was a mere 
coincidence, since I find that myelocytes and erythroblasts are very 
commonly present in cachexia from any cause. 



SARCOMA. 

In general the effects of sarcoma are like those of cancer, but 
ivorse. Great ansemia and higher leucocyte counts are the rule. 
The literature of the subject is rather scanty. 

Bed Cells. — Hayem in a case of osteosarcoma counted the red 
cells at 663,400 per cubic millimetre. 

Laker^ describes an " abdominal cystosarcoma " in which two 
counts of red cells showed 2,800,000 and 2,500,000. 

Von Limbeck ^ in 1 case found 1,118,000, and in another 2,240,- 
000. Both were osteosarcomata. 

Sadler* in 3 cases found 2,710,000, 3,637,000, 4,500,000. 

Eieder^ in 3 cases (all osteosarcomata) found 1,846,160, 3,700,- 
000, and 3,995,000. 

The Massachusetts General Hospital blood counts include 19 
cases in which the red cells were counted (see Table LXVIIL, A and 
B), the average being 4,400,000, not nearly so low as that recorded 

' Wiener med. Presse, December, 1894. 

2Wien. med. Woch., 1886, p. 926. Loc. cit., p. 343. 

4Xoc. aY., pp. 38, 39. aY., pp. 98, 100. 



SARCOMA. 



395 



by other observers ; still low counts occurred (2,706,000, 2,637,000, 
3,842,000). 

The qualitative changes in the red cells consist (as in cancer) of 
the " degenerative " changes (deformities in size and shape, englob- 
ular changes) present in marked cases, and the presence of nucle- 
ated corpuscles, when cachexia is marked. 

Table LXVIII., A. — Sarcoma with Leucocytosis. 



Age. 



46 

32 

24 
41 
68 
48 

57 

Adult. 



30 



Red 
cells. 



4,188,000 
4,312,000 
4,000,000 

2,706,000 
4,560,000 



4,700,000 

2,630,000 
2,900,000 
4,352,000 
3,842,000 
6,200,000 



4,180,000 



4.512,000 
5,422,000 



5,480,000 



Wbite 
ceils. 



98,000 
25,000 
44,600 

56,000 
17,000 



23,900 
33,400 
37,900 
41,200 
33,000 
36,000 
40,200 
55,400 
16,000 
19,000 
24,000 
21,000 
13,600 
61,100 
16,(X)0 
Marked 

In- 
crease. 
13,000 
16,250 
15,180 
18,000 
Great 

In- 
crease. 
Great 

in- 
crease. 
13,200 
6,700 
26,100 
28,500 

19,980 
14,100 
10,200 
18,400 
21,600 
16,600 



Per 
cent 
h£emo- 
globin, 



65 



Remarks. 



Polynuclear cells, 90.2 per cent. 
Polynuclear ceils, 80.9 per cent. 
Polynuclear cells, 70 per cent (infant of twenty 

months). 
Sarcoma of kidney. Autopsy. 
Melanotic sarcoma of all abdominal organs (bone 

metastasis ? ) . November 30tb, 1895. Differential 

count of 600 cells : Polynuclear, 71 per cent ; 

small lymphocytes, 11 ; "large lymphocytes, 5.2 ; 

eosinophiles, 12.4 (!); myelocytes, 4. 
December 7th. 
December 13th. 
December 19th. 

December 22d. 
December 26th. 
January 14th. 
January 28th. 

Sarcoma of abdominal organs. 

Three days later. Autopsy. 

General sarcomatosis. 

One week later. Autopsy. 

Sarcoma of kidney. 

Sarcoma of lung, etc. Autopsy. 

Sarcomatosis. 

Differential count of 700 cells : Poly., 70 per cent ; 

lymphocytes, 22 ; eosinophiles, 1 ; myelocytes, 7. 

Sarcomatosis. 
Melanotic sarcoma of abdominal organs. 
One week later. 

Sarcoma of abdominal organs. 

Osteosarcoma (thigh). Differential count of .500 

cells : Poly., 74 per cent ; small lymphocytes, 19; 

large lymphocytes, 6 ; eosinophiles, 1. 
Sarcoma of abdominal organs. Differential count 

of 800 cells : Poly., 84 per cent ; lymphocytes, 

15.5 : eosinophiles, 5. 
Sarcoma of abdominal wall. 

Neck. 

One month later. Polynuclear, 89 per cent ; lym- 
phocytes, 9.8 ; eosinophiles, 1.2. 
Neck. Autopsy. 
Ceecum. 

Abdominal wall. 
December 2d. Adrenal. 
December 5th. 
December 16th. 



Small tumors are often without any effect on the blood (see 
Table LXVIII. , B). According to v. Limbeck ' this is oftener true 
than in cancer. 

^ Loc. cit. 



396 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table LXVIII., B. — Sarcoma without Leucocytosis. 



Age. 



Red 
cells. 



5,380,000 
4,980,000 
4,946,000 
4,953,000 
5,390,000 



4,388,000 



White 
cells. 



8,300 
9,000 
9,000 
6,000 
6,100 
7,600 
6,500 
5,600 
9,800 
5,100 

5,700 a.c. 

8,600 p.c. 



Per 
cent 
haejio- 
globin. 



Remarks. 



Sarcoma of testicle. 

Sarcoma of ovary. 

Osteosarcoma of shoulder. 

Small recurrent sarcoma of groin. 

Glands. 

Ovary. 

Cutaneous. 

Kidney operated. 

Kidney operated. 

Retroperitoneal. Polynuclear, 66 per cent : lym- 
phocytes, 33.4 ; eosiiiophiies, .6. Reds good. 



Hcemoglohin. — Eeinbacli's^ 20 cases ranged between 23 and 75 
per cent, averaging 52 per cent. 

Bierfreiind ^ in 29 cases found variations between 40 and 75 per 
cent. 

Yon Limbeck's 2 cases had 28 and 48 per cent respectively. 

Eieder's^ 4 cases showed at the beginnmg of treatment 29, 56, 
57, and 65 per cent respectively, but in 1 case the haemoglobin went 
down gradually while under observation until it reached 6 per 
cent ( !), the lowest point, Eieder says, that he has ever seen in any 
disease. 

Sadler's^ cases showed 33, 45, and 78 per cent. 

In the 16 cases of Table LXVIII. in which this point was noted, 
the average is 59 per cent. 

On the whole, the coloring matter seems to be more diminished 
than in most cases of cancer. 

Leucocytes. — The following tables, slightly modified from v. 
Limbeck, show the important points. 



No. 


Observer. 


Diagnosis. 


Count. 


1 




Hay em. 


Osteosarcoma. 


11.250 


2 




Alexander. 




52.700 


3 , 








16.430 


4 








16,275 






it 


(( 


17.050 


5 








15.900 








(( 


15,570 


6 








13.020 



^ Loc. cit. 



Loc. cit. 



""Loc. cit. 



^Loc. cit 



SARCOMA. 



397 



No. 


Observer. 


Diagnosis. 


Count. 


7 

8 

9 

10 

11 

1 o 

13 

14 

15 

16 


Alexander. 
Rieder. 

a 
li 

V. Limbeck. 
Reinbacli. 
Mass. General Hospital. 


Osteosarcoma. 

I 


10,950 
12,090 
11,248 
12.700 
10,900 
9,100 
8,000 

QO AAA 

26,800 
20,000 
13,000 
21,000 
9,000 






Average, 


17,000 ± 




No. 


Observer. 


Diagnosis, 


Count. 


1 . 

2 

3 

4 

5 

6 

7 

8 

9 

10 , 

11 

12 


Hay em. 
Alexander. 

u 

u 
u 

V. Limbeck. 

;( 

Sadler. 
(( 

(( 


Lymphosarcoma. 


11,700 
19,910 
19,530 
11,696 
11,470 
10,540 
55,100 
38,000 
10,800 
33,248 
19,299 
9,044 






Average, 


20,000 + 




No. 


Observer. 


Diagnosis. 


Count. 


1 

2 

3.. 

4 

5 

6 

7 


Rieder. 

Reinbach. 
Mass. General Hospital. 


Melanosarcoma. 

li 


41,600 
28,500 
22,300 
25,000 
8.000 
37,900 
13,000 






Average, 


25,100 -f- 



For other sarcomata, see Table LXVIII., A and B. 
On the whole, leucocytosis appears to be more constant and of 
greater extent in sarcoma than in cancer. 



398 



SPECIAL PATHOLOGY OF THE BLOOD. 



Qualitative Changes. 

1. The increase of polymorphonuclear leucocytes which we find 
in most forms of leucocytosis is not always present in sarcoma^ and 
seems to be less frequent than in cancer (see Cases o, 11, 14, Table 
LXVIIL). 

As in cancer, it may be present when no increase in the total 
leucocytes is to be found, and may be the only indication of any dis- 
ease in the organism. 

2. A few cases are on record in which a large percentage of 
eosinopliiles has been present. 

Eeinbach found 48 per cent of eosinopliiles in a case of sarcoma 
of the neck with sloughing and ulcerative endocarditis, the percent- 
age continuing over 40 for several weeks. ^ Autopsy showed sarco- 
matous nodules in the bone marrow. In another case, a tumor of 
the abdomen, the eosinopliiles were 10.5 per cent, and in two others 
8 per cent. 

A case of apparent sarcoma of the abdominal organs (no autopsy) 
at the ]\[assacliusetts General Hospital in January, 1896, had 12.4 
per cent of eosinopliiles. 

Such cases should certainly make us think of bone metastases, 
and Neusser speaks of osteosarcomata as being accompanied by 
eosinophilia, but the CAddence is as yet fragmentary. 

^ Palma (Deut. med. Woch., 1892) reports lymphocytosis in sarcoma. 
^ The full coimts are as follows : 



April 4th, 1892. May 20tli, 1892. 

Red cells 5,396.000 Red cells 4,512.000 

AYhite cells 120,000 (I) White cells. 52,000 

Haemoglobin 60 per cent. Haemoglobin 55 per cent. 



DIFFERENTIAL COUXTS. 





April 4th. 


May 1st. 


May 20th. 


May 26th. 


Lymphocytes 


Per cent. 
48 
48 

2.7 

1 


Per cent. 
51 
46 
2.32 
.68 


Per cent. 
55 -|- 
42 
1.5 
.64 


Per cent. 
51 + 
44 + 
3.2 
.8 



SARCOMA. 



399 



3. 2Iijelocijtes. — Eeiiibach's case just described had a low per- 
centage of myelocytes. 

The following cases illustrate the same point : 

Case I. is a case of sarcomatosis in a man in whom sarcomatous 
nodules were distributed all over the internal organs and in the skin. 
A differential count of 700 white cells showed in his case : 

Per cent. 



Typical myelocytes (over 15/^) 2 

Small myelocytes (under 15//) 5 

Lymphocytes 23 

Polynuclear neutrophiles 70 

Eosinopliiles 1 



The autopsy showed no special lesions in the spleen, glands, or 
bone marrow, except those due to the sarcomatous nodules. 

Case II. — Sarcoma of the abdominal wall. A differential 



count of 800 cells showed : 

Per cent. 

Polynuclear neutrophiles 84. 

Lymphocytes 10.5 

Large lymphocytes 5. 

Eosinophiles 2 

Myelocytes 3 

Case III. (Xo. 5, Table XL VIII., A).— Six hundred cells con- 
tained : 

Per cent. 

Polynuclear neutrophiles 71. 

Lymphocytes 16.2 

Eosinophiles 12.4 

Myelocytes . 4 



Summarij of Blood Changes in Malignant Disease. 

1. Small, slow-growing tumors and the early stages of all tumors 
may have no effect on the blood appreciable by our present methods 
of examination. 

2. In advanced cases the red corpuscles often become thin, light, 
and pale, and finally their number may be greatly decreased, the 
counts running sometimes as low as in pernicious anaemia. In this 
respect, as in others, sarcomata seem to injure the blood more than 
cancers. 

3. The color index is always below 1, but is rarely as low as we 
find it in severe chlorosis. 



400 



SPECIAL PATHOLOGY OF THE BLOOD. 



4. Normoblasts and megaloblasts (the latter being in the minor- 
it}^) may occur, the former even in the absence of severe anaemia. 
Deformities in size and shape are common. 

5. Leucocjtosis is present in the cachectic end-stages of many 
cases, but is frequently absent in small tumors of slow growth and 
without' metastases. The polymorphonuclear cells are often rela- 
tively increased. 

6. Fibrin is not increased. 

Diagnostic Value. 

1. When we are dealing with an obscure, deep-seated disease, 
if hemorrhage is excluded, the presence of persistent leucocytosis 
suggests suppuration or malignant disease (rather than tuberculosis 
or syphilis, for example), and excludes any simply functional or 
hysterical affection. The ahsence of leucocytosis, however, does not 
exclude malignant disease, though it makes suppuration very un- 
likely. 

2. Between malignant disease and suppuration — if the other 
signs and symptoms do not decide — there may be nothing in the 
blood to decide. In decided pysemia we may get pyogenic cocci from 
the blood by culture, but a negative result would not exclude the 
suppurating focus. 

The ahsence of any increase of fibrin in the blood speaks against 
suppuration, and therefore in favor of malignant disease ; but the 
presence of increased fibrin network is not decisive either way, as 
it may be met with in connection with neoplasms, though more 
common in suppuration. 

3. Between malignant disease and hemorrhage a marked anaemia 
favors the latter, provided the case is a recent one ; for the anaemia 
of malignant disease is comparatively slow to develop. The leuco- 
cytes give no help. 

4. Between cancer and ulcer of the stomach, if there has been 
no recent hemorrhage, leucocytosis favors cancer; but its ahsence is 
of no weight either way. 

The haemoglobin is said to decrease steadily in cancer, while in 
ulcer it tends to return toward normal after the cessation of hemor- 
rhage. 

The presence and persistence of digestion leucocytosis speak 
against cancer, and its absence in favor of cancer. It must be 
remembered, however, that any variety of catarrh or dilatation 



SARCOMA. 



401 



(should such be present) can also prevent digestion leucocytosis, 
and that the latter is not invariably present even in health. 

5. Between cancer of the liver or bile ducts on the one hand and 
sinqyle gall-stone colic or gall-stone obstruction, the presence of leu- 
cocytosis favors cancer. As usual, however, its absence does not 
exclude cancer, and we must bear in mind that gall stones with cho- 
langitis may raise the leucocyte count as much as cancer. Simple 
cysts or echinococcus cysts cause no leucocytosis, nor does syphilis 
of the liver. 

6. The appearance in the blood of large numbers of eosinophiles, 
myelocytes, and nucleated corpuscles during the course of a malig- 
nant disease points to a bone metastasis. 

7. When a leucocytosis which has disappeared after removal of 
a neoplasm reappears, we may expect recurrence of the growth 
shortly. 

8. A steadily increasing leucocytosis in a case of malignant 
disease points to a rapidly growing tumor or to the occurrence of 
metastasis. 

9. Between malignant disease and pernicious anaemia, the diag- 
nosis rests on the following points : 

I. Color index low in malignant, apt to be high in pernicious 
anaemia. 

II. Leucocytes often increased in malignant, dimmished in per- 
nicious anaemia. 

III. Lymphocytes often decreased in malignant, increased in 
pernicious anaemia. 

ly. Average size of red cells often decreased in malignant, and 
often increased in pernicious anaemia. 

V. If nucleated red corpuscles are present the normoblasts are in 
a majority in malignant disease, and in a minority in pernicious an- 
aemia. 

10. The presence of leucocytosis is against the benignness of any 
tumor. 

11. When no actual increase of leucocytes is present, an increased 
percentage of the polymorphonuclear variety among those present 
may have the same significance as a leucocytosis. 



26 



CHAPTER XI. 



BLOOD PARASITES. 

Examination for the Plasmodium Malaria and its Products. 

I. Tims for Examination. — It is often stated that the organism 
is most easily found during the chill. But this is not the writer's 
experience. During a chill it is often difficult and sometimes im- 
possible to find the organisms. Eight hours before or after a chill 
is the most favorable time (Thayer), although parasites have been 
found as late as forty-eight hours after the last chill. During the 
chill many organisms retire to the internal organs. 

The number of organisms varies a great deal. In some cases 
they are present in every field of a one -twelfth immersion lens, 
while in others we may find only one after an hour or more of pa- 
tient search. In some cases of coma Ewing had to search one and 
two hours before finding a single parasite. In the majority of the 
cases occurring near Boston, it needs but a few minutes' search to 
find them if the blood be taken within twelve hours before or after 
a chill, and provided no quinine has been lately given. Occasion- 
ally in mild cases the organisms are very scanty ; and it may be al- 
most impossible to find any. Theobald Smith agrees with Ewing 
that when the parasites are scarce, especially when they are of the 
small unpigmented form, a prolonged search through fresh blood 
has frequently proved negative, although a few minutes sufficed for 
the discovery of one or more minute parasites in the stained speci- 
men. The quartan and sestivo-autumnal forms of malaria are so 
rare in New England that I shall not attempt to describe in detail 
the parasites found in them, but shall confine myself mostly to the 
parasites of common tertian and double tertian fevers with which I 
am personally familiar. 

II. Method of Examination. — A slide of fresh blood is prepared 
as above described (pages 6-8) and examined with a one-twelfth 
immersion lens.^ Lower powers should not be used, although in 

^ In cold weather both slide and cover should he warmed before using. 
Indeed this is always well, as it makes the corpuscles spread better. 



BLOOD PARASITES. 



403 



skilful hands they are often sufficient. Portions of the slide in 
which the corpuscles do not overlie each other should be chosen for 
examination. As we pass the slide along beneath the lens it is well 
to be on the lookout for any specially large or specially pale corpus- 
cle. Such a one will catch the eye if we are on the watch for it, 
even though the slide is being passed along very rapidly, and all 
such should be carefully examined. 

Another thing to watch for is anything black or dark brown. If 
the slide is not perfectly clean, or if the cover-glass has touched the 
skin in collecting the blood, there will often be black spots which 
make us pull up short and examine, only to find that they are bits 
of dirt. This loses time, and hence, as above noted, the impor- 
tance of care and cleanliness in the earlier stages of the process. 

Besides any strikingly pale or swollen corpuscle or any black 
dots, we should be on the lookout for any movements in the field. 
The movements of Mtiller's "blood-dust" (see page 60) are often 
mistaken by beginners for those of the malarial organism. Their 
greatly smaller size and extra corpuscular position serve to distin- 
guish them in most cases. I have sometimes thought I saw pig- 
ment in these bodies. If, as Stokes believes, the "blood-dust" is 
derived from the leucocytes, it is possible that they might carry out 
with them some pigment ingested by the leucocyte. 

Flagellate bodies may be studied in fresh specimens, if possible, 
on a warm stage. Usually they appear only after the lapse of ten 
to twenty minutes from the larger tertian or crescentic aestivo-au- 
tumnal organisms. The addition of a little water or salt solution 
may facilitate the escape of the parasite from the red cell and the 
formation of fiagella. 

Ewing finds that the moist chamber may be secured in a Petri 
dish with tightly fitting vaselined cover. Wet blotting-paper placed 
in the dish furnishes the necessary moisture. Specimens spread on 
slides or covers may be kept moist for ten to twenty minutes in such 
dishes, and flagellation proceeds with moderate rapidity. 

A simple method is as follows : Cut an opening one-half by one 
inch in a piece of thick blotting-paper and moisten the paper in hot 
water. Spread two glass slides rather thickly with fresh blood, lay 
the blotting-paper on one slide, cover the cut opening by the other, 
specimen side down, and slip a rubber band about both. After fif- 
teen or twenty minutes the slides and paper may be separated and 
the two specimens dried. 



404 



SPECIAL PATHOLOGY OF THE BLOOD. 



III. The 3Ialarial Organism . — {a) It practically is never to be 
seen outside the corpuscle. Most malarial organisms are to be found 
within the corpuscle, and onhj there. ' 

For those who have not examined many specimens of malarial 
blood it is a very difficult thing to find the organism at this stage of 
its growth, and the number of mistakes in diagnosis is very large. 
I always look with great suspicion on any report of malarial blood 
as containing only "hyaline forms." 

In the later stages, when the organism has become well pig- 
mented, there is nothing that at all resembles it, and those who 
have seen and watched it a few times can hardly mistake anything 
else for it. Not so with the so-called " hyaline " or youngest form 
of the organism. Personally I think the name ''hyaline bodies" is 
responsible for a part of the mistakes. We are led to expect some- 
thing more shinj^ and refractile than the organism really is, and so 
are misled by the brilliant white circles to be found at the centre of 
many normal corpuscles under certain conditions of light and partial 
drying up. Time and again I have been asked to look at malarial 
organisms (always the "hyaline" forms), and found nothing more 
than one of these effects of light which can be found in any normal 
blood, if the conditions are right. There are certain marks by 
which we can exclude these artifacts from consideration: 

I. They are generally far too numerous to be malarial organisms. 
One usually finds a dozen or more in a field which would be almost 
unheard of with the plasmodium malarise. 

II. They are generally in the centre of the corpuscle, while the 
young malarial organism is almost never at the centre. 

III. They are almost invariably round, the malarial organism 
being generally more irregular and branching. 

IV. They seem to increase and diminish in size as v/e focus up 
and down upon them, while the malarial organism only grows dim- 
mer or clearer. 

V. They are, as before mentioned, more brilliantly white and 
shiny than the malarial organism, which has often a faint tinge of 
yellow, although much paler than the surrounding corpuscle sub- 
stance. 

VI. Their edges are sharper, the malarial organism often fading 
off very gradually into the corpuscle color. 

^ Except degenerate forms, free flagellse, and spores at the moment of seg- 
mentation {rarely to be seen). Crescents and ovoid bodies are intercehular. 



MALARIAL ORGANISM^. 

(After Wright & Brown.) 



PLATE V. 





Fig. 1.— Young Non-Pigmented, Hyaline Form 
of the ^stivo-Autumnal Parasite in a Red 
Blood Corpuscle. 



Fig. 2.— Adult Tertian Parasite. 




Fig. 3.— An Adult Tertian Parasite, with Rod-Shaped Pigment, in a Red Blood Corpuscle in the 
Right of the Figure, and in a Corpuscle in the Left of the Figure a Young Pigmented Ter- 
tian Parasite and a Signet-Ring Form of the ^stivo- Autumnal Parasite. Thus there is an 
infection with two kinds of parasites. 



BLOOD PARASITES. 



405 



VII. (a) Their movement is different. The malarial organism 
is not at all the only thing to be seen moving in the blood, as has 
sometimes been stated. The red corpuscles have the Brownian mo- 
tion, and as they begin to crenate often move very actively. But 
their motion is very different from that of the hyaline malarial 
organism, for the latter changes both its shape and its position in 
the corpuscle quite rapidly, while the motion of the light space in 
an ordinary red cell is a wavy undulation of the outlines back and 
forth without any considerable change of shape. 

(b) As soon as the organism g|ts any pigment (and there are 
very few times in the cycle of a malarial case when there are not 
some pigmented organisms present), the active rapid motion of the 
black pigment dots is unlike anything else seen in the blood, and 
when once recognized can never be forgotten or mistaken. It is 
only when the pigment has ceased moving (owing to the death of 
the organism) that the' differentiation between dirt and malarial 
pigment becomes difficult. 

Sometimes it is really difficult to distinguish motionless pigment 
in a malarial organism from dirt even on careful scrutiny. The 
best way is to get a fresh slide when the pigment is in motion. 

To any one fairly familiar with the appearance of pigmented 
forms of malarial organisms, failure to find them in a case of mal- 
aria is due generally (1) to too thickly spread a layer of blood, the 
corpuscles overlying each other; (2) to not looking long enough; 
(3) to.lack of proper light. 

(c) The next stage, that of segmentation, is less commonly seen 
than are those just mentioned, and is only to be satisfactorily ob- 
served by using a warm stage (vide supra, page 8) and spending con- 
siderable time on the watch for it. Aroand the central pigment mass 
we may sometimes see in ordinary specimens (without warm stage) 
the faint outlines of a group of small spherical, colorless bodies 
(vide Fig. 2, 9, Plate I.) which are the new generation of young 
organisms. 

Now we should expect that with the next step in the process we 
should find these young plasmodia free in the plasma or entering a 
fresh set of red corpuscles. But in the peripheral circulation this; 
is rarely if ever observed. Thayer in his immense experience has 
never seen them. The next evidence we have of the organism is as 
a "hyaline " body inside the corpuscle again. 

Almost all stages of the growth of the plasmodium which we 



406 



SPECIAL PATHOLOGY OF THE BLOOD. 



can watch in the blood drawn from the peripheral circulation take 
place within the corpuscle. It is true that as the pigmented organ- 
ism gets toward its full growth, and before the granules have begvm 
to gather at the centre, we may find it very difficult to find any 
trace of corpuscle substance around the margin of the j^lasmodium. 
Sometimes we see a ring of non-pigmented glistening white sub- 
stance outside the moving black dots (see Fig. 2, 7, Plate I.) stand- 
ing out light against the darker ])lasvia. This I suppose to be the 
remains of the corpuscle. It is not described or pictured in the 
standard works on the subject. ^ 

Occasionally we do find pigmented bodies wholly outside the 
corpuscle, either partly or fully grown. In the intracorpuscular 
forms the distinction between plasmodium and corpuscle substance 
is not, I think, so sharp and clear as one would be led to expect 




Fig. 36.— Flagellate Malarial Organisms. (After Thayer.) 



from the plates in standard works. With average eyes and lenses 
the outline of the organism, as distinguished both from its pigment 
granules and the surrounding corpuscles, is not easy to see. It is 
the moving pigment granules that attract our notice. 

The youngest form of the tertian parasite seen in the red cell is 
identical in appearance with the spore of the parent rosette. It is a 
compact spheroidal, or slightly oval, or irregular body, about 2 ii 
in diameter. It shows an outer rim of basophilic protoplasm in- 
closing a single large nuclear body, which is achromic to methylene 
blue, but stains readily in hsematoxylon or by Nocht's method, and 
which is usually inclosed or accompanied by a clear achromatic sub- 
stance, termed by Gautier "the milky zone." 

In the fresh condition these bodies are noticeably refractive, es- 
pecially the nucleus, change their position but rarely their shape, 
and are never pigmented. 

The young tertian ring : Within a few hours after the chill the 
parasite is usually found to have assumed a somewhat characteristic 



MALARIAL ORGANISMS. 

(After Wright & Brown.) 



PLATE VI. 




Fig. 4. Fig. 5. Two Tertian Parasites in One Red 

Figs. 3 and 4.— Adult Form of Tertian Para- Blood Corpuscle, 

site in a Degenerated Red Blood Corpuscle. 
The pigment is seen in the form of rods. 




Fig. 6.— An Adult Tertian Parasite with Central Vacuole and Rod-Shaped Pigment in a Distorted 
Red Blood Corpuscle at the Left of the Figure. At the right of the figure an adult parasite 
with its pigment gathered together in clumps. This is a tertian parasite in early stage of 
segmentation. The dark spots at the periphery of the parasite represent the remains of the 
red blood corpuscle which it has invaded. 



BLOOD PARASITES. 



407 



ring shape. These bodies measure from 3-4 ix in diameter, and 
there is not much increase in bulk for six or eight hours. The ter- 
tian ring is rarely as geometrical or delicate as the sestivo-autumnal 
signet ring. The nuclear body of the tertian ring is its most char- 
acteristic feature, appearing as a rather large, achromatic, highly 
refractive body, after methylene blue, but staining intensely with 
hseniatoxylon and by Nocht's method. 

Comparison of the Tertian and Mstivo- autumnal Rings. 

(1) According to Ewing, the nuclear body and the chromatin 
mass of the young tertian parasite are achromatic to methylene blue, 
which densely stains the nucleus of the aestivo- autumnal organism. 

(2) The shape and contour of the tertian ring is usually coarse 
and irregular, but the sestivo-autumnal ring is geometrically circu- 
lar, more delicate, with extremely line bow, and usually with a 
typical signet-like swelling. 

(3) One or two grains of pigment are almost invariably found in 
the early tertian ring, but are with nearly equal constancy absent 
from the sestivo-autumnal signet ring. 

(4) The tertian ring is usually pigmented before the chromatin 
becomes subdivided, while the chromatin of the sestivo-autumnal 
ring is always subdivided before the appearance of pigment. 

(5) The infected cell is usually swollen from the moment of in- 
fection by the tertian spore, and commonly shrunken when harbor- 
ing the sestivo-autumnal ring. 

Large tertian rings : After a period of six to eight hours the 
ring is usually found to have developed an outgrowth which is 
actively amoeboid in the fresh condition and appears in stained 
specimens as a tongue-like protrusion or turban-shaped mass at- 
tached to one segment of the ring. The nuclear body meanwhile 
increases slightly in size, jirojecting into the ring, and the chroma- 
tin divides into several large granules. 

At this period occurs the greatest amoeboid activity of the para- 
site, and in some severe infections the organism may be found fixed 
in the height of its amoeboid excursions. There the ring persists, 
but the body of the parasite is strung out into a number of slender 
threads with nodal thickenings. 

Tertian spheroidal bodies : During the second quarter of the 
•cycle, the body and nucleus of the parasite develop rapidly in size, 
amoeboid motion and figures gradually diminish, and pigment is 



408 



SPECIAL PATHOLOGY OF THE BLOOD. 



abundantly deposited in the form of dark brown or yellowish grains, 
showing in the fresh state active vibratory motion. The cell in- 
creases in size and its haemoglobin diminishes. Toward the end of 
twenty-four hours or possibly somewhat later, the parasite occupies 
three-fourths of the swollen cell, in the form of a spheroidal or 
elliptical, homogeneous body, the outer portion of which contains 
most of the pigment. 

Full-grown tertian ijarasite : The third quarter is occupied by 
the continued growth of the parasite in the form of a large homo- 
geneous, richly pigmented body, which finally occupies at least four- 
fifths of the swollen cell. 

F re-segmenting bodies usually begin to appear in the blood eight 
to ten hours before the chill. The pigment is gathered in a re- 
duced number of coarse grains or spindles which lie in the body of 
the parasite, in a position determined by that of the new multiple 
nuclei. 

Tertian rosettes are usually seen in the circulation three or four 
hours before the chill, most abundantly just before the chill, rapidly 
disappearing after the chill. 

TJie eai'liest form of the oestivo-autumnal ijarasite is often distin- 
guished from the tertian by the shrinkage of the cell, low refrac- 
tive index, and it is never pigmented. 

The oistivo- autumnal signet ring is a very characteristic shape 
assumed by the parasite at a very early period. It is noted that in 
some cases the rings fail to exhibit this thickening but remain of a 
uniform but very fine calibre throughout. Multiple infection with 
the young rings is very common ; three parasites are often found 
in the same red cell, and occasionally four. The signet-ring forms 
frequently reach a diameter of 4 ; beyond this size, when persist- 
ing in the finger blood, the growth of the parasite produces an ir- 
regular body in which the outline of the rmg becomes more or less 
obscure. The full development of the large signet rings appears to 
require about twenty-four hours. In the majority of cases the ring- 
forms seen in the peripheral blood fail to shoAv any trace of pig- 
ment. 

The later forms of the wstiro- autumnal parasite are rather rarely 
seen in the peripheral circulation. 

The crescentie bodies : On the fourth to sixth days of any but 
initial paroxysms of the ses-tivo- autumnal infection the peripheral 
blood may contain red cells infected by spheroidal, oval, elliptical. 



MALARIAL ORGANISMS. 

(After Wright & Brown.) 



PLATE VII. 




Fig. 7.— An Adult Tertian Parasite in tbe 
Same Stage as Fig. 6, with its Pigment Col- 
lected in a More Compact Manner at Its 
Central Part. The irregular dark zone at 
its periphery is the remains of the red 
blood corpuscle in which the parasite has 
developed. 




Fig. 9.— Same as Fig. 3. 




■si' 



Fig. 8.— Completed Segmentation of a Tertian 
Parasite. Each of the dark rounded bodies 
represents a young parasite. The pigment 
of the parasite from which they are derived 
is shown, as well as the faint outlines of 
the red blood corpuscle in which they are 
contained. 









■« 











Fig. 10.— a Young Parasite and an Adult 
Parasite w^th a Vacuole, in One Red Blood 
Corpuscle. 



BLOOD PARASITES. 



409 



or small crescentic bodies which represent the early forras of the 
sexual cycle of the parasite. The relation of these forms to the 
young amoeba is not clear. A remnant of haemoglobin surrounds 
the crescent on all sides. The membrane or thickened outer border 
of the red cell is closely applied about the convex side of the cres- 
cent, while across the concavity it stretches loosely like a halter. 

In the centre of the crescent is a sharply marked, light -blue 
staining or a chromatic area of variable size, containing the chro- 
matin, and usually also the pigment. 

The long persistence of crescents in the blood and their resist- 
ance to quinine are matters of common clinical observation. 

Dr. J. H. Wright has kindly permitted the use of many of the 
accompanying photographs of the malarial parasites (see Plates 
v., yi., VIL, VIII., and IX.). 

Flagellate bodies: When blood containing crescents is allowed 
to stand in the air or under a cover-glass for a few moments some 
of the crescents slowly assume the spheroidal form, active vibratory 
oscillations of pigment granules begin, and soon, from one or more 
points, pseudopodia shoot out with active lashing movements. 
These flagella continue their movements for some time, changing 
their position actively, their shape slowly, while some may be seen 
to break off from the body and swim off through the plasma. 

Tertian flagellate bodies develop from the full-grown tertian par- 
asites in much the same way as from the crescents. Quartan para- 
sites develop flagellate bodies very similar in appearance to those of 
the sestivo-autumnal type. 

Exactly why and under what conditions it shows or fails 
to show these appendages is not known.' They are about two 
or three times as long as a red corpuscle and one-sixth or one-eighth 
as wide. Sometimes there is pigment dotted along the flagellum 
itself, and then we can make it out more easily. Its distal end is 
especially apt to be pigmented, and by the help of this pigment we 
make out that it is bulbous, while similar swellings can sometimes 
be seen at other points along the flagellum (see Fig. 37). As the 
pigmented end is sometimes all that we can see of it, this gives rise 
to the appearance of a very small, actively locomotive pigmented 
body free among the corpuscles, and its course may be followed 
through several fields. 

^ McCaflum has recently offered interesting evidence that tliey are sexual 
organs. 



SPECIAL PATHOLOGY OF THE BLOOD. 




Fig. 37.— Flagellate Malarial Organisms. 
(After Manson's photographs.) 



Allien the flagella have 
ceased movmg, their presence is 
generally detected, if at all, by 
an irregular line of pigment 
dots about 20 ix long, which 
will be shown by careful focus- 
sing to be contained within a 
nearly transparent membrane. 

Very often we find a leuco- 
cyte in process of closing round 
the flagellated parasite. Man- 
son has lately succeeded in 
staining the flagellse, and the 
accompanying photographs are 
from his stained specimens. 

Pigmented leucocytes, con- 
taining the whole or part of 
malarial organisms or simply 
blocks or granules of black 
pigment, are usually to be found 
in the blood near the time of 
the chill. The pigment is to 
be carefully distinguished from 
the granules present in most 
leucocytes, which in certain 
lights look quite dark even if 
unstained, dark enough to be 
mistaken for pigment by the 
untrained eye. Careful focus- 
sing and changing the light will 
easily determine which we are 
dealing with, provided we are 
familiar with the appearances 
of leucocytes in the fresh un- 
stained blood. In certain 
forms of the disease in which 
the organisms themselves retire 
to the internal organs, the 
presence of pigmented leuco- 
cj'tes may be the only evidence 



MALARIAL ORGANISMS. 

(After Wright & Brown.) 



PLATE VIII. 




Fig. 11.— Crescentic Form of ^stivo- Autumnal Parasite in a Red Blood Corpuscle, which is Much 
Distorted by It. The pigment is seen in the centre of the parasite in the form of rods. 




Fig. 13.— In the Right of the Figure is a Crescentic Parasite Distending a Red Blood Corpuscle. 
In this and Figs. 13 and 14 the hlue-stained parasite is made to appear darker than the eosin- 
stained red blood corpuscles, by changing the character of the light used for illumination of 
the specimen. The deeper staining poles of the parasite is shown in this and the succeeding 
figures. In the left of the figure a tertian parasite in a red blood corpuscle is shown. There 
was, therefore, a double infection in this case. 



BLOOD PARASITES. 



411 



of the disease to be found in the peripheral blood and is therefore 
of the greatest importance. 

Hitherto I have spoken of the apj)earance of the parasites in 
the fresh unstained blood, this being by far the simplest, easiest, 
and surest way of finding them and the only way of studying their 
development. In cases in which we cannot make a microscopical 
examination at the bedside, we can sometimes preserve the organ- 
ism alive between slide and cover-glass, until we can get it to the 
nearest microscope, even if this takes several hours. I have car- 
ried specimens in my handbag a whole m_orning and yet found 
the pigment of the malarial parasite in motion at the end of that 
time. Warm weather favors this. When it is necessary to keep 
the specimen some time before examination, it is best to paint on 
-the slide a ring of vaseline or any gummy substance, and allow the 
drop of blood to spread out inside this ring so that the margins of 
the cover-glass are glued to the slide by the oily substance and the 
entrance of air is prevented. The cedar oil ordinarily used for im- 
mersion lenses answers the purpose very well. Both slide and 
cover should be gently warmed before the drop of blood is spread 

Many physicians who cannot possibly carry a microscope about 
with them can easily find room for a few slides and cover-glasses, 
and they may be of great service. 

When specimens have to be sent by mail, or for long distances, 
or in cold weather, we have to fall back on dried specimens prepared 
as described on page 43, provided always that a bedside examina- 
tion is impossible. These can be stained by one of the following 
methods : 

I. Leave the specimen for half an hour or more in equal parts 
of ether and absolute alcohol, dry them in the air, stain for from 
one-half to five minutes in a one-half -per-cent solution of eosin in 
sixty-per-cent alcohol, wash in water, dry and stain one-half to one 
minute in concentrated watery solution of methylene blue; wash 
again in water, dry in filter paper, and mount in Canada balsam. 
With this stain the nuclei of leucocytes and the malarial parasites 
are stained blue, while the red corpuscles are very pale yellow and 
almost transparent. This transparency of the red discs may be 
taken advantage of when the films either from accident or design 
are thick. The stained parasites can be recognized even if covered 
with a layer of red discs. 

After drying thoroughly in the air the malarial parasite stains 



412 



SPECIAL PATHOLOGY OF THE BLOOD. 



best after fixation in ninety-live to ninety-seven per cent alcohol 
for fifteen to thirty minutes. The addition of ether to the alcohol 
secures no advantage (Ewing). 

II. Thioiiui Hue is a good malarial stain, especially for the 
young forms. Cover-glass films are to be fixed for one minute 
in a one-per-cent solution of formalin in ninety-per-cent alcohol, 
dried with filter paper, washed quickly in absolute alcohol, again 
dried with filter paper, and finally stained for thirty seconds in the 
following mixture, which should stand a week or more before it is 
used : 

Tliionin (saturated sol. in 50-per-ceut alcohol) 1 part. 

Carbolic acid, 2 per cent 5 parts. 

Wash in water, dry in filter paper, and mount in balsam. 

Yet on the whole I have had better success with the eosin and 
methylene blue despite its difiiculties. 

Modified Futcher and Lazcar method : ''Fix the specimens five 
minutes in ninety -five-per-cent alcohol to 100 c.c. of which has been 
added, just before using, 1 c.c. of formalin. Stain one to three 
minutes in the following mixture : Saturated alcoholic solution of 
thionin, 20 c.c. ; 20-per-cent carbolic acid, 100 c.c. The fixing 
solution must be used fresh, and the staining fluid must be at least 
one week old. The rings are then densely stained, and the speci- 
mens do not fade." 

III. The ordinary Ehrlich triacid mixture with Hewes' after- 
stain gives good results. The organism itself stains blue with this 
mixture and stands out against the yellow of the corpuscle, the pig- 
ment looking as it does in the live parasite. It is sometimes con- 
venient to use the same stain for the differential count and the mal- 
arial organism, as for instance when we have only one cover-glass 
preparation in a case of doubtful diagnosis. Fixing the specimen 
in alcohol and ether is here far better than heat; otherwise the 
technique is as above described under Triple Staining (page 44). 

If the organisms are fairly numerous and the technique is good 
we can find them by this method even in preparations months old. 
In general, however, it is very inferior to the examination of the 
live organism m the fresh blood, and gives many more chances for 
error. 

IV. Ewing states that he has never failed to secure a good re- 
sult by the following procedure : 

"1. To 1 ounce of polychrome methylene blue (Griibler) add 5 



MALARIAL ORGANISMS. 

(After Wright & Brown.) 



PLATE IX. 




Fig. 13.— Crescentic Parasite Distending a Fig. 14.— Ovoid Form of the iEstivo-Autumnal 
Red Blood Corpuscle. Parasite Distending a Red Blood Corpuscle. 

A portion of the corpuscle projects above 
the parasite and is much distorted. The 
dark line around the parasite also repre- 
sents the remnants of the corpuscle. 

(After Goldhorn. ) 




Fig. 15.— Tertian Fever. Young form, so- 
called ring-body. Bloodplatelet on cell 
to left. 




Fig. 16. —Tertian Fever. One so-called Fig. 17.— Tertian Fever. Maturing organ- 

"ring" form; one matured organisms, isms with loosened-up chromatin. Large 

the infested cell showing degeneration. lymphocyte and platelets. 



BLOOD PARASITES. 



413 



drops of three-per-cent solution of acetic acid (U. S. P., thirty- 
three per cent). 

" 2. Make a saturated one-per-cent watery solution of methylene 
blue, preferably Ehrlich's (Griibler) or Koch's, dissolving the dye 
by gentle heat. This solution improves with age, and should be at 
least one week old. 

"3. Make a one-per-cent watery solution of Griibler' s ivatery 
eosin. 

" The mixture is prepared as follows : 

''To 10 c.c. of water add 4 drops of eosin solution, 6 drops of 
neutralized polychrome blue, and 2 drops of one-per-cent methyl- 
ene blue, mixing well. The specimens, fixed in alcohol, or by heat, 
are immersed, specimen side down, for one to two hours, and will 
not overstain in twenty-four hours. The density of the blue stain 
may be varied to suit individual preferences. The above propor- 
tions need not be rigidly followed, but the polychrome solution 
should be accurately neutralized, and the staining mixture should 
be deep blue." 

Goldhorn has recently succeeded in digesting methylene blue 
with saturated solution of lithium carbonate so as to develop in it a 
large proportion of the red chromatin- staining principle. This 
fluid, neutralized by acetic acid, not only stains the chromatin rap- 
idly (fifteen to sixty seconds), but demonstrates better than has yet 
been done early and extreme granular degeneration of the infected 
and other red cells. Goldhorn' s fluid, ready for use, can be obtained 
from New York dealers.' 

So much for technique. 

We often hear reports of fruitless search for the parasite in the 
blood of malarial patients, but the regularity with which they are 
found at all the larger hospitals and by all practised observers in 
this and other countries leaves no doubt that they are to be found in 
every case during some portion of the cycle. The practice of taking 
blood during a chill contributes, I believe, to the number of unsuc - 
cessful endeavors to find the organism; as mentioned above, this is 
the worst, not the best time to look for them. Too thick a layer of 
blood between slide and cover accounts for some failures, as I have 
found in personal experience. 

No doubt, in many cases in which we fail to find the organism 
in supposed malaria a faulty diagnosis is the reason. Many of the 
^ See Trans. New York Path. Soc, February, 1901. 



414 



SPECIAL PATHOLOGY OF THE BLOOD. 



cases in which latent malaria is supposed to have " come out " after 
a surgical operation are exploded by the negative examination for 
parasites and the positive indications of pus-j^ocketing which are 
afforded by a marked leucocytosis (never present in simple malaria) ^ 
and the fact of insufficient wound drainage is often disclosed in this 
way. Whenever we see the leucocytes increased we begin to doubt 
the existence of an uncomplicated malaria; if, furthermore, we see 
no signs of any pallor of the corpuscles we doubt the presence of 
malaria still more, as there is no more rapid deglobularizer than the 
malarial organism. 

How long after a chill the organisms may still be found in the 
peripheral blood is difficult to decide, but certainly they can be 
found any time within twenty-four hours after the last chill, unless 
quinine has been given, and sometimes even if it has been given.' 

Other Changes in the Blood. 

Bed Corpuscles. — The following is from Thayer's remarkable 
monograph : 

" A reduction in red corpuscles follows each paroxysm ; these 
reductions are more marked after the early paroxysms than after 
those occurring later. When a certain degree of anaemia has been 
reached the losses per paroxysm are much less. Wren the number 
of corpuscles is reduced to 2,000,000 or 1,000,000 there is little 
tendency toward a further fall ; sometimes there may be slight rises 
in the curve between the paroxysms ; often, however, the number of 
corpuscles remains stationary for weeks. 

" In pernicious cases the number of corpuscles may fall between 
paroxysms." Kelsch'has seen the count decrease to as small a 
number as 500,000 per cubic millimetre. The diminution is greater 
the longer the disease lasts and the more intense its manifestations 
are 

In Swing's Montauk series, there were "no less than nineteen 
cases in which the changes of the progressive pernicious type had 
been established in a period not longer than ten weeks." 

There can be no doubt that the tendency of the sestivo-autumnal 
parasite is to be massed in the bone marrow. The excessive de- 
mands on red-cell production render pernicious malaria an extremely 
favorable condition for this disturbance of the marrow and specific 
megaloblastic changes. 



MALARIAL ORGANISMS. 

(after Qoldhorn. ) 



PLATE X. 




Fig. 18.— Tertian Fever. Fig. 19.— Tertian Fever. Marked stippling 

of infected corpuscle. Single chromatin 
body. Achromatic zone very distinct. 




Fig. :iO.— Tertian. Fig. 21. — Intracorpuscular Segmenting 

Body in Tertian Fever. Stippling of cor- 
puscle. 



Fig. 33.— Segmentation of Malarial Organ- Fig. 23.— Tertian Fever. Double infection 

ism in Tertian Fever. Stippling of cor- of corpuscle, one organism segmenting, 

puscle. 



BLOOD PARASITES. 



415 



During the paroxysms, particularly the earlier ones, the red 
cells tend to increase in number. 

In tertian and quartan fevers there is a rapid and almost com- 
plete restitution of the corpuscles during the afebrile period. 

In sestivo-autumnal fevers the number of red cells bears a direct 
relation to the number of organisms. Crescentic bodies seem to 
have no influence on the number of red cells. 

When after a paroxysm the number of corpuscles has been 
greatly diminished the succeeding paroxysm may be followed by a 
slight reduction only or even by an increase. 

Bignami and Dionisi distinguish three types of post-malarial 
ansemia : 

1. Ordinary secondary anaemia, but with leucopenia instead of 
leucocytosis ; such cases usually end in recovery. 

2. Anaemia practically identical with pernicious anaemia, megalo- 
blasts being present, and ending fatally. 

3. Anaemias which are progressive, because the bone marrow can- 
not compensate for the losses of corpuscles. 

The rapidity of the diminution in red cells may be very great. 
Kelsch's count of 500,000 cells per cubic millimetre, mentioned 
above, was after thirty days' illness. G-rawitz has seen a loss of 
4,000,000 cells in six days. 

Qualitative changes are those of severe secondary anaemia, de- 
formities in size and shape, normoblasts, occasional megaloblasts in 
the worst cases, motility in the "pale, ghostly" cells. 

Hcemoglohin. — The loss of haemoglobin bears usually a direct 
relation to the number of parasites in the blood. As a rule, the 
corpuscles and haemoglobin are diminished proportionally (color 
index = 1) but sometimes the haemoglobin is reduced dispropor- 
tionately. 

In convalescence the restitution of haemoglobin is often incom- 
plete; persons living in malarial districts have often a slightly 
smaller percentage of haemoglobin than those living elsewhere. 

The rapid diminution in haemoglobin is a valuable point in dif- 
ferential diagnosis between malaria and typhoid or pneumonia. 

White Cells. — The number of leucocytes is usually subnormal, 
but a slight increase is shown at the beginning of the paroxysm. 
Following this increase there is a rapid decrease continuing through- 
out the paroxysm. The small number of leucocytes is to be seen at 
the end of the paroxysm when the temperature is subnormal. From 



416 



SPECIAL PATHOLOGY OF THE BLOOD. 



this time it shows a gradual increase until the beginning of the next 
attack (Billings). 

In a general way the white cells follow the same course as do 
the red. 

The differential count shows a lymphocytosis whenever the white 
cells are subnormal, the larger forms of lymphocytes being espe- 
cially numerous, while the polymorphonuclear cells and eosinophiles 
are scanty. 

In the severer sestivo-autumnal paroxysms Kelsch found that 
the leucocytosis of pernicious malarial attacks often consists in 
marked lymphocytosis ; this Avas also observed by Ewing. 

The extent of the leucocjrtosis varies between 10,000 and 35,000 
cells, the latter having been observed by Kelsch shortly before 
death in a comatose patient. 

In four cases of post -malarial anaemia Billings found quite 
marked leucocytosis. 

The occurrence of pigmented leucocytes has already been men- 
tioned. 

Grawitz and others have noticed an increase of eosinophiles in. 
post-malarial anaemia. I have frequently found small percentages 
of myelocytes, three per cent being the highest in my experience. 

MALARIAL H^MOGLOBIN^EMIA. 

During the paroxj^sms of this form of the disease, the number 
of the red cells is much diminished, rouleaux are not formed, marked 
poikilocytosis with nucleated forms is observed. The leucocytes 
are increased. The regeneration is very swift, twenty-four to forty- 
eight hours being usually sufficient to re-establish normal con- 
ditions. 

Ttphoid Fever axd Malaria. 

"After the first week when the typhoid fever has become fully 
established, active sporulation of malarial parasites is extremely 
rare" (Ewing). 



CHAPTER XII. 



DISEASES DUE TO ANIMAL PARASITES, 

FILARIASIS. 

Although most commonly found in tropical countries, one spe- 
cies of the iilaria sanguinis hominis is not very uncommonly found 
in various parts of the United States. Any case of chylous urine 
or elephantiasis should lead us to make a careful examination of the 
blood for the filaria. There are at least four species of iilaria, one 
of which is present in the blood chiefly at night, another chiefly 




Fig. 38,— The Filaria Sanguinis Hominis. Thf head, curled up, is seen at the right of the cut, 
the tail at the left. Instantaneous photomicrograph. Four hundred diameters magnlflcation. 



during the daytime, and ano'ther continuously. Only the filar la 
nocturna has thus far been seen in America (Fig. 38). 

In examining for the filaria a slide of the fresh blood is pre- 
pared in the usual way, hiit after 8:30 (y doc'k in the evening, and 
examined at once. The embryo of this parasite (which is what we 
find in the human blood) is from one-ninetieth to one-seventieth of 
an inch in length, i.e., about fifty times the diameter of a red cell, 
and about the width of a red corpuscle. Seen in the blood it re- 
tains its vitality and motile power for a considerable time, so that 
its motions may continue a week or more between slide and cover- 

^ In persons who sleep in the daytime and work at night the habits of the 
filaria are said to become reversed, so that it appears in the peripheral circula- 
tion chiefly in tlie daytime, and is to be looked for then. 
27 



418 



SPECIAL PATHOLOGY OF THE BLOOD. 



glass. Cold has little effect upon it, even freezing temperature 
failing to do more than make the movements slower. 

A distinction can generally be made out betAveen the embryo 
proper and its sheath (see Fig. 39). From this sheath the embryo 
escapes when in the blood of the mosquito, which insect acts not 
infrequently as intermediary host and conveys the parasite indi- 
rectly from man to man through the medium of water. After suck- 



Fig. 39.— Tail of Filaria, Showinrr Prolongation of the Sheath beyond the End of the Embryo 
Itself. Magnified 800 diameters. 

ing in the organism with the blood the mosquito lays its eggs and 
dies in some neighboring pond or stream whence the filaria again 
gains access to men. 

It is a long, slender, snake-like, gracefully shaped worm, and 
when alive its activity is so great that measurements and observa- 
tions of its structure cannot be made till it is paralyzed by ap- 
proaching death (Fig. 40). 

Posteriorly it tapers for one-fifth its length down to a very 
sharp point. The extreme end of the tail often looks as if articu- 
lated, for it does not harmonize with the general curve of the body, 



FILARIASIS. 



419 



but lies bent at an angle. Toward the head it tapers very slightly, 
and when alive a " ponting " movement as if of breathing can be 
seen at its very extremity. About the middle of the body a granu- 
lar aggregation can be made out along the central axis of the ani- 
mal. Except for this granular portion the parasite is so translucent 
that it is not easy to make it out at first. The distinction of body 
and sheath mentioned above appears as a " clear space " at each 
end of the body {vide Fig. 39). After the motions have ceased 




Fig. 40.— The Movement of a Single Filarla during Four Successive Exposures of One-fifth of i 
Second Each, the Entire Series Occupying less than Five Seconds. Magnified 800 diameters. 



it becomes darker and traces of transverse striation may be seen 
(Fig. 41). 

It has no locomotive power and confines itself to wriggling in 
the same spot. Saussure^ says he has watched them " fighting with 
each other for hours." 

The head of the filaria is said by some authorities to be supplied 
with feelers or flagella, and Manson describes what he calls a 
" cephalic armature " or fang (Fig. 42) . 

The same organism can sometimes be found in the chylous 

' Philadelphia 3Iedical News, June 28th, 1890, where he reports twenty 
cases seen in Charleston, S. C. 



420 



SPECIAL PATHOLOGY OF THE BLOOD. 




Jig. -i:.'.— Hfucl ui Filaria Maguilled l/iOi) Diameters. The blur ia frout uf tlie head may be due 
to the motion of flagella. 



FILARIASIS. 



421 



urine, but not every case of chyluria is due to the filaria sanguinis 
hominis. In a considerable portion of cases no such organism is 
to be found. 

Henry' succeeded in staining the parasites intrcv vitam by giving 
the patient considerable doses of methylene blue internally for some 
weeks. Only a faint bluish tinge was imparted, however, to the 
organism by this method. 

For finding the parasite it is best to use a low power, not an 
immersion lens, and the whole of several slides should be looked 
over. 

Specimens can be dried and preserved for staining provided we 




Fig. 43. 



-Head of Filaria Overlapping a Red Corpuscle. The appearance might be mistaken for 
the cephalic end of a sheath. 



do not heat them over a lamp or pass them through a flame. Man- 
son^ stains with eosin and mounts in "glycerin jelly" (Fig. 43). 

Several other species have been observed in England in negroes 
from the Congo Eiver, but not hitherto in America. But as it fre- 
quently is to be found in persons who have no symptoms whatever, 
it may well be that some of these other species would be found 
here if one took the trouble to seek out natives of Southern China 
(one out of every ten of whom carries about the filaria in his blood) , 
or of Central Africa, or other tropical regions. 

1 Med. News, May 2d, 1896. 

^ The "Filaria Sanguinis Hominis," by Patrick Manson, M.D., Amoy, 
China, 1883. 



422 



SPECIAL PATHOLOGY OF THE BLOOD. 



SPIROCHETE OF RELAPSING FEVER. 

During the febrile paroxysms of relapsing fever, and for one or 
two days before them, Obermeyer and others have found constantly 
present in the peripheral circulation a parasite whose length aver- 
ages about six times the diameter of a red corpuscle. Even under 
high-power lenses it is a mere thread in width, curled upon itself 




Fig. 44.— SpirochEetes of Relapsing Fever in Human Blood. 



like a corkscrew and actively motile, so that in examining the blood 
with a low power we get a " peculiar impression of disturbance 
among the red cells. 

The number of twists in this spiral-shaped organism varies a 
good deal, and one of its motions consists in contracting and ex- 
tending itself like a spiral spring. It can thus multiply its own 
length three or four times. It has also a delicate, wavy, but rapid 
motion along its long axis. The whole thread, or a part of it only, 
may have these motions. Further, the whole parasite has power 
of locomotion apparently independent of the currents in the blood 
plasma of a slide and cover-glass specimen. Its locomotion is slow 
compared to the movements above described. Particularly in the 
blood post mortem they are apt to wind themselves into each other 
so as to seem much larger than they actually are, and sometmiss 



SPIROCHETE OF RELAPSING FEVER. 



423 



a large " nest " of them may look like a leucocyte, except for the 
fine wavy threads which can be seen in motion at the periphery of 
the mass. 

The number present in the blood is very much smaller at the 
beginning of a paroxysm than after the second day. During the 
first few hours of a febrile period Mocyntkowsky could find only 
one spirochaete in ten or twenty microscopic fields, while later on 
he saw twenty or thirty of them in a single field. There are usu- 
ally more parasites with each successive paroxysm. 

Blood taken from different parts of the body often shows a great 
difference in the number of organisms to be found. The life his- 
tory of a single parasite seems to be very short, but they multiply 
with the greatest rapidity. Albrecht has seen them so increase 
within six hours that whereas at first he saw only a few in the 




Fig. 45.— Spirochaetes of Relapsing Fever in Human Blood. 



whole slide he later found many in each field. As the spirochaete 
dies, its movements get languid, and finally it breaks up into small 
granular bits (spores?). 

Between paroxysms the spirochaete s are not found, but there are 
to be seen peculiar highly ref ractile globules compared by v. J aksch 
to a diplococcus. The latter author believes that he has seen these 
develop into the spirochaete at the beginning of a paroxysm and 
hence believes them to be spores. 



4 



424 



SPECIAL PATHOLOGY OF THE BLOOD. 



/ 












^wvv '-^v:: ^--^^'A-v- 










FIG. 46. 



1 



Fig. 47. 

Spirochtetes of Relapsing Fever. 



SPIROCHETE OF RELAPSING FEVER. 



425 



This spirochsete is found in all cases of relapsing fever and in 
no other known disease, so that like the plasmodium malarias it is 
pathognomonic and of the highest 
importance. 

Anaemia and leucocytosis (during 
the paroxysm) are among the sec- , _ ^ -^'^ 



ondary results of the presence of this ^ . Sj\)j;' 

parasite in the blood. 

Boeckman reported that the red ■ 



cells sink during, and for one to two ^ 
days after, the attack, increasing ' 6^^'^ 

somewhat in the afebrile periods. 

Laptschinsky, Heidenreich, and 
Boeckmann all noted considerable / ^-^^ 

leucocytosis. Laptschinsky men- r-""^-^ 

tioned the presence of a very large * ^---^^ ^/ ; \ 

number of coarsely granular leuco- ' V i ' / ? 

cytes. ^' 

A certain resemblance has been ' - ' - 

noted between the spirochaete and > 
a free flagellum broken off from a 
malarial parasite, but the clinical 
history and the presence or absence 
of other evidence of malaria in the 

blood would easily decide the ques- / ; ' ^ 

tion of diagnosis. , 

Techniqite of Examination. — As 
in looking for the malarial organism, 

it is best to examine the blood fresh \ 

between a slide and cover-glass (^;ic?e . 

siq)ra, page 7) and to use an oil- ' , 

immersion lens. In dried specimens \ - — - 

the organism can be stained with ^^'^ 

fuchsin, but it is much more difficult 

, Fig. 48.— Leucocytes Containing 

to recognize than ni the fresh blood. Spirochgetes. 

The spirilla stain well with aniline 

dyes, and Karlinski succeeded in demonstrating flagella with some 
individuals. Concentrated solution of methylene blue stains all 
spirilla in two to five minutes. Phagocytosis (see Fig. 48) can 
easily be watched in the peripheral blood. 



426 



SPECIAL PATHOLOGY OF THE BLOOD. 



DISTOMUAI H^MATOBIUM. 

Bilharz found this parasite post mortem in the large internal 
veins (portal, splenic, mesenteric, etc.), but as it has never been 
seen in the peripheral circulation its clinical importance is thus 
far nil. 



AX^MIA DUE TO IXTESTIXAL PARASITES. 

The bothriocephalns latus, ankylostoma duodenale, and a few 
other parasites are capable of j)roducLng by their presence in the 
intestine a very severe anaemia, which may be indistinguishable 
from pernicious anaemia. Bothriocephalns anaemia has been studied 
by Schaumann in a monograph (Berlin, 1894, Hirschwald) which 
is the very acme of careful, conscientious work and eclij)ses entirely 
the fragmentary observations of earlier writers. Ankylostomiasis 
has been thoroughly studied by B. K. Ashford of the United 
States army in Porto Eico, by Askanazy, Eogers, Sandwith, and 
others. 

BOTHRIOCEPHALrS AXJE]\nA. 

The presence of the bothriocephalns latus in the intestine of 
man is usually accompanied by anaemia. In certain cases, how- 
ever, under conditions not at all clear at present, there is j)roduced 
an anaemia of tlie severest type, differing from ordinary pernicious 
anaemia only in its curability through the expulsion of the worm. 

Schaumann* s magnificent study of the blood of 38 cases resulted 
in the following data : 

1. Bed cells at time of first examination : 

2,000,000 to 2,500,000 in 1 case (2.150,000) 
1,500.000 " 2,000.000 9 cases 
1,000.000 " 1,500.000 " 17 " 
500,000 " 1,000,000 " 10 " 

Under 500,000 " 1 case (395,000) 

38 

Average of all = 1.290,000 



BOTHRIOCEPHALUS ANEMIA. 



427 



2. Hcemoglohin (first test) : 

30 to 40 per cent in 7 cases. 
20 " 30 " " 18 " . 
10 " 20 " " 13 " 

38 cases. 
Average, 25 per cent. 

3. Color index: Less than 1 in 8 cases (0.9 to 0.99), more than 
1 in 30 cases. Average 1.09. 

4. Average diameter of red cells 7.4 microns (slightly above 
normal) . 

5. Poikilocytosis marked, but its degree is not parallel with the 
degree of anaemia. 

6. Kouleaux formation always defective or altogether absent. 

7. Polychromatophilia and stippled red cells common. 

8. Nucleated red cells present in all cases examined for them — 
26 —but without parallelism with the degree of anaemia. Megalo- 
blasts predominated in over half the cases. In 5 cases megaloblasts 
only appeared; in one case normoblasts only. In the other 20 cases 
both types were present. Mitoses were found in 2 cases. 

Leucocytes usually normal or subnormal in number. 

Differential count practically as in pernicious anaemia. 

The eosinophiles are noted as " very scanty " in 25 cases and " ap- 
parently somewhat increased " in 1 case. [This is in sharjD contrast 
with the eosinophilia usually present in ankylostomiasis (^vide page 
IIG.)] A few myelocytes were noted in 2 cases with leucocytosis. 

Blood plates diminished. 

So far the figures refer to untreated cases at the worst stage of 
the disease. Five-sixths of the cases were entirely and aj^parently 
permanently cured in about two months by the expulsion of the 
worms. Blood counts at the time of leaving the hospital showed: 

In 3 cases about 2,500,000 red cells 
2 " " 3,000,000 " • " 
2 " " 3,500,000 " " 
16 " " 4,000,000 " " 
4 " " 4,500,000 " " 
4 " " ' 5,000,000 " 
Average 4,680,000 (16 cases still higher) with 70 per cent haemoglobin. 

Thirteen of these were followed up after discharge, and in these 
a full restitutio ad integrum occurred. 



428 



SPECIAL PATHOLOGY OF THE BLOOD. 



ANKYLOSTOMIASIS (UNCINARIASIS). 

The first careful observations of the blood of which I have 
knowledge are those of Zappert in 1892. ' The following counts 
are reported by him : 



Per cent 

Case. Red cells. Haemoglobin. 

1 5,180,000 50 

2 4,384,000 40 

3 4,350,000 50 

4 4,272,000 30 

5 3,728,000 45 

6 3,372,000 40 

7 3,272,000 25 

8 3,244,000 40 

9 3,204,000 40 

10 2,040,000 25 

11 2,496,000 25 



The most striking fact here is the low color index. The anaemia 
is of moderate grade. 

Mliller and Rieder^ were the first to note the eosinophilia which 
later observations have shown to be so frequent. They record 8.2 
per cent and 9.7 per cent in 2 cases of the disease. Zappert re- 
fers to 2 cases with 17 per cent of eosinophiles. 

Rogers'' compares the anaemia produced by the ankylostoma 
with that due to malaria and with the blood of the average native of 
Assam, where his studies were carried on. His results are shown 
in the following table : 





Red cells. 


White cells. 


Hi^moglobin. 


Healthy Assamese 


4,734,000 


7,325 


67 per cent. 




2,000,000 


1,600 


31 




1,145,000 


5,338 


15 



Rogers does not refer to the percentage of eosinophiles. 
In 1894 Bucklers* reported the following counts : 

1 Zappert: Wien. klin. Woch., 1892, No. 24. 
^Muller and Rieder: Arch. f. khn. Med., vol. xlviii. 
3 Brit. Med. Jom-nal, 1900, p. 539. 
^Bucklers: Mimch. med. Woch., 1894, No. 2. 



ANKYLOSTOMIASIS. 



429 





Case I. 


II. 


III. 


lY. 


V. 


YI. 


Eed cells 

White cells 

Htrmos:lobin 

Eosiuopliiles 

Polvnuclear 

Lymphocytes and transi- 


3,649,000 
13,000 

16^ 

46 

37 


15,000 

74 
22 


3,954,000 
20,600 
45.0^1 
53.6 
22.3 
25.1 


10. 4^ 

46 
43.6 


21^ 
22 
53 
25 


25.0^ 
21.2 
32.2 
46.6 



Leichtenstern (referred to by Ehrlich and Lazarus) illustrated 
the behavior of the eosinophiles in the presence of a secondary in- 
fection by this case : 

" In the blood of a very anaemic, ahnost moribund patient with 
ankylostomiasis there were found, in 1897, 72 per cent of eosino- 
philes. The patient contracted a croupous pneumonia, and in the 
high febrile period of the disease the eosinophiles sank to 6 and 7 
per cent, rising again after the termination of the pneumonia to 54 
per cent. After removal of the worms the eosinophiles fell at once 
to 11 per cent. 

" In 1898, when the faeces contained but very few ankylostomata 
. . . the eosinophiles amounted to 8 per cent." 

At my request Dr. Bailey K. Ashf ord, first lieutenant and assist- 
ant surgeon in the United States army, has written the following 
account of his studies in the ankylostoma anaemias of Porto Eico. 
His results will soon be more fully reported in monographic form. 

ANKYLOSTOMIASIS. 

By Bailey K. Ashford, M.D., 
first lieutenant, assistant surgeon, u. s. a. 

The Blood ix Gross. 

The gross appearance of the blood in severe cases shows a great 
diminution in color and fluidity of the drop taken for examination. 
The statement that it resembles water in which fresh meat has been 
washed holds true in many instances. Lender the microscope there 
is observed a great paucity of cellular elements and a frequent ab- 
sence of rouleaux. 



430 



SPECIAL PATHOLOGY OF THE BLOOD. 



QUAXTITATIYE ChAXGES. 

Red Corimscles. 

There is a progressive tendency to profound oligocythgeniia, even 
to as great an extent as is found in severe cases of pernicious anse- 
mia, and to an even greater oligochronisemia. 

Eighteen cases were examined in Ponce, Puerto Pico, at the 
fiekl iiospital for storm sufferers of August 10th, 1899. Of the eigh- 
teen cases the average count was 1, 776,176 red cells per cubic mil- 
limetre on admission; the lowest recorded was 668,888, and the 
highest was 3,084,440 per cubic millimetre, both these counts hav- 
ing been taken after three weeks' observation ; 10 cases on admission 
gave counts ranging from 1,000,000 to 2,000,000; 7 cases between 
2,000,000 and 3,000,000; one case fell below 1,000,000. 

Sandwith studied in Egypt 173 cases. Of these only 3 exceeded 
4,000,000 red cells per cubic millimetre; twenty-three per cent 
were found to have between 3,000,000 and 4,000,000; 46.8 per 
cent lay between 2,000,000 and 3,000,000, and 28.3 per cent had 
less than 2,000,000. His minimum count was 930,000, and his 
aA'crage count of hospital cases was 1,290,000 per cubic milli- 
metre. 

Counts as low as 500,000 have been recorded. In my series the 
abrupt rise and fall in blood count was astonishing, and error could 
hardly have been made, as the two counts which were made at each 
examination tallied very closely in each instance. Three cases giv- 
ing respectively 1,200,000, 1.484,440, and 1,600,000 fell in about 
three weeks to 801,104, 687.776, and 668,888 red cells per cubic 
millimetre. Two rose from 697,776 and 2,064,664 to 2,664,440 and 
3,084,440 per cubic millimetre. 

We must make allowances for intensity of infection, virulence of 
infection, immunity, etc., but ordinarily the red blood count in typ- 
ical cases will present from 1,500,000 to 2,500,000 per cubic milli- 
metre. Some of the Puerto Pican cases demonstrate a severe type 
of the disease, and notes of other cases there show that counts 
nearer 1,000,000 are frequently encountered. 

•This tremendous loss of blood is seemmgly well borne for a 
longer period than one would expect, and men with one-fourth their 
normal quota of red blood corpuscles subject themselves to quite 
hard labor. 



ANKYLOSTOMIASIS. 



431 



White Corijusdes. 

There is probably no true leucocytosis in the disease. As it is 
an affection liable to be complicated by other diseases producing 
leucocytosis, we can easily explain many of the classical references 
to the "leucocytosis of ankylostomiasis." An examination of the 
chart of the Ponce cases will show this more plainly. 

The average number of white corpuscles in these cases was 
about 7,000 per cubic millimetre. One case with lobar pneumonia 
had 18,000 leucocytes per cubic millimetre, and another with ab- 
scess of the liver had 11,000. Excepting one case (with 12,700), 
all the rest were well below 10,000, and the average of 17 uncom- 
plicated cases was about 6,000. The lowest record was 1,500 per 
cubic millimetre. 

Hcemoglohin. 

The haemoglobin is more reduced than the red blood count. In 
Sandwith's cases the haemoglobin average was 26 per cent. The 
average of 18 of the Ponce cases gave about 21 per cent of haemo- 
globin and an average color index of 0.62 for 17 of them.^ The 
lowest reading was 10 per cent, the highest 30 per cent. Twice 
only the color index rose above 1.0; once to 1.43, and once to 1.09. 

Qualitative Changes. 

(«) Keel Corpuscles. 

Poikilocytosis was present in 16 of 17 of the Ponce cases. 
Macrocytes are exceedingly common in this disease, as are also 
microcytes, and the deformities of the cells in advanced cases are 
as varied and as frequent as in pernicious anaemia. 

Polychromatophilia was marked in only 4 cases, bat irregularity 
in staining is a prominent sign. 

Xormohlasts and Merjalohlasts. 

xNTormoblasts and megaloblasts are apparently not so frequently 
met with as in pernicious anaemia, and there is seldom a case re- 
ported as having a preponderance of the latter. Among the Ponce 
cases only one patient presented an equal number of each. The 

^ The von Fleischl apparatus was used, and the capillary tube was three 
times filled that chances of an error might be minimized. 



432 



SPECIAL PATHOLOGY OF THE BLOOD. 



average number of normoblasts per cubic millimetre was about 35; 
of megaloblasts, about 7. Five cases had no normoblasts and 12 
bad no megaloblasts, while 5 had neither. 

White Corpuscles. 

In the ' differential count the polymorphonuclear neutrophiles 
gave an average of 63 per cent. The loAvest noted Avas 40 per cent, 
and the highest 74 per cent. The normal was not disturbed save 
when the percentage of eosinophiles rose ; then that of the poljmior- 
phonuclear neutrophiles sank proportionately to the rise in the 
former. As seen by the chart of the Ponce cases, addition of the 
percentages of the two varieties gives us a normal polymorphonu- 
clear neutrophile count. 

There was no lymphocytosis noted. The average was about 
19 per cent for small lymphocytes and 7.5 per cent for the large 
variety. 

The eosinojjhiles sJioiv a remarkable increase in some cases and 
some increase in nearly all. The average eosinophile count in the 
Ponce cases was 10. 3 per cent ; 6 showed a percentage at or below 
4. The highest was 40 per cent, the lowest IJ per cent. Three 
were respectively 13, 31, and 40 per cent. 

Atlas,' of Vienna, reports a case with 16 per cent of eosino- 
philes, and Kwasnicki," of Galicia, one with 24 per cent of these 
cells. The polymorphonuclear neutrophiles in each instance were 
respectively 51 and 49 per cent of the total differential count. 

These facts would seem to suggest (1) that the blood in this 
disease is modified by some toxin, as post-hemorrhagic anaemia has 
not this characteristic of eosinophilia, and trichiniasis, a disease due 
to another nematode parasite, has. Indeed, it was this eosino- 
philia and the coincidence of the discovery of high eosinophilia by 
Brown, of Johns Hopkins University, in the first-named affection 
that led the writer to suspect an animal parasitic origin in the cases 
of anaemia at Ponce. 

(2) That these cases had presented at some period of the infec- 
tion a higher eosinophilia, especially those bearing a lower percent- 
age. The cases with the three higher counts were of comparatively 
acute character. 

Myelocytes are occasionally reported, a notable case being that of 
Blickhahn,'" of St. Louis, Mo. One of the Ponce cases showed 
a few. 



ANKYLOSTOMIASIS. 



433 



Schedule of Blood Examinations in Nineteen Cases at Ponce, 

Porto Eico. 



Date. 


Current number. 


Red cells. 


Percentage of 
haemoglobin. 


White 
cells. 


Percentage of poly- 
morphonuclear 
leucocytes. 


Percentage of smal 
leucocytes. 


Percentage of largt 
leucocytes. 


Percentage of 
eosinophiles. 


Normoblasts per 
cubic millimetre. 


Nov. 4th.. 
Nov. 23d.. 


1 


1,530,116 
1,880,000 


20 
16 


6,800 


65 


21 


9 


5 


26 


Nov. 3d . . 
Nov. 23d.. 


2 


697,776 
2,664,440 


20 
23 


7,960 


59 


17 


15 


9 


144 


Nov. 4th.. 
Nov. 23d.. 
Nov. 5th.. 
Nov. 23d.. 
Nov. 6th. . 
Nov. 23d.. 


3 
4 
5 


1,533,112 
1,973,328 
1,200,000 

801,104 
1,484,440 

687,776 


22 
23 
15 
17 
10 
14 


2,000 
4,200 
6,000 


64 
64 
64 


22 
23.4 
24 


8 
6 
8 


6 
6.6 
4 


8 
109 
13 


Nov. 6th.. 


6 


2,193,328 


23 


8,800 


65 


26 


8 


IM 


123 


Nov. 7th.. 


7 


1,633,328 


17 


5,600 


60 


23 


5 


12 


11 


Nov. 7th.. 
Nov. 23d.. 
Nov. 7th.. 
Nov. 23d . . 


8 
9 


2,064,664 
3,084,440 
1,271,104 
^,520,000 


23 
31 
14 
24 


4,800 
7,800 


74 
60 


17 
17 


6 
6 


3 

17 


38 
30 


Nov. 7th. . 
Nov. 23d.. 
JNOV. oth.. 
Nov. 8th. . 
Nov. 9th.. 


10 

11 
12 
13 


1,600,000 
668,888 
l,oUl),UUU 
2,296,656 
1,268,888 


17 
13 

25 
30 
20 


1,500 

4,600 
7,680 
6,800 


72 

69 
52 
63 


20 

22 
26 
17 


4 
7 

12 
7 


4 

2 
10 
13 


6 
9 


Nov. 9th.. 


14 


2,440,000 


25 


11,000 


50 


10 


9 


31 




Nov. 9th.. 
Nov, 9th.. 


15 
16 


2,353,328 
2,934,444 


17 


12,700 
5,200 


73 

72 , 


17 
20 


4 
5 


6 
3 


io 


Nov. 10th. 


17 


2,140,000 


23^ 


18,000 


40 


12 


8 


40 


36 


Nov. 12th. 


18 


Unknown. 


30 


9,000 


60 


16 


10 


10 


135 


Nov. 20th. 


19 


1,560,000 


16 


2,400 


72 


10 


5 


13 





So 



15 



10 



Remarks. 



Poikilocytosis, Polychro- 
matophilia, many micro- 
cytes and macrocytes. 

Poikilocytosis. Polychro- 
matophilla, many macro- 
cytes and microcytes. 

Poikilocytosis. No rou- 
leaux, 

Poikilocytosis. Polychro- 
matophilia. 

Poikilocytosis. Slight ten- 
dency to rouleaux forma- 
tion ; macrocytes and 
microcytes, latter pre- 
dominate over former. 

Poikilocytosis. No ten- 
dency to rouleaux for- 
mation. 

Poikilocytosis. Many ma- 
crocytes and microcytes ; 
slight rouleaux forma- 
tion ; marked chromato- 
philia. 

PoikUocytosis. Rouleaux 
formation good. 

Has elephantiasis Arabum, 
but I cannot identify 
the fllaria as yet. Micro- 
cytes predominate over 
macrocytes. Good rou- 
leaux formation. 

Poikilocytosis. 

Poikilocytosis. 

Poikilocytosis. Rouleaux 

formation good. 
Poikilocytosis. Rouleaux 

formation slight ; has 

abscess of liver. 
Poikilocytosis. Rouleaux. 
Tertian malarial parasites 

found. Rouleaux good. 
Poikilocytosis. Rouleaux 

good. I believe this man 

to have been suffering 

from pneumonia at time 

of examination. 
Poikilocytosis. Rouleaux 

formation good. 



The course of the convalescence is remarkable for its brevity in 
acute cases, but when serious secondary affections are engrafted on 
the original disease it is very slow. The chief difficulty seems to 
result from damaged intestine and heart. One of the writer's 
patients at the beginning of treatment was in imminent danger of 
28 



434 



SPECIAL PATHOLOGY OF THE BLOOD. 



siicoum"bmg to the anaBmia. He was a boy of about ten years of 
age and liis case acute. AYitliin six weeks he was transformed into 
as ruddy a specimen as could be expected, on the administration 
of the usual thymol treatment. 

Of Sandwith's 173 cases he states that the least gain on treat- 
ment was 310,000 red cells per cubic millimetre. Another case, that 
of a boy, gained in one month seven pounds in weight and 2,208,000 
red cells per cubic millimetre. Ten patients gained over 2,000,000, 
one of them 2,542,000. His average gain of all cases in haemo- 
globin was 22 to 32 per cent. 

Agnoli'' reports a case in which there was a gain of 2,168,000 
red cells per cubic millimetre and of twenty-six pounds in weight 
in thirty-five days. 

Authors Cited. 

1. Daniels: The British Guiana Medical Annual, 7th issue, 1895. 

2. Be van Rake : Journal of Pathology, November, 1894. 

3. Lussano: "Contributo alia patogenesi dell' anemia la anchylostomiasi." 
Ki vista Clinica, 1890, No. 4. 

4. Arslan: "L'anemie des mineurs chez les enfauts." Rev. mens, des 
mal. de I'enf., 1892, p. 555. 

5. Bohland : " Uber die Eiweisszersetzung bei der Anchj'lostomiasis. " 
Miiucli. med. Wochenschr. , 1894. No. 46. 

6. Saudwith : " Observations on Four Hundred Cases of Anch ylostomiasis, " 
written for the 11th International Med. Congress at Rome, 1894. 

7. Atlas : " Anchylostomum Duodenale. " The Med. Press and Circular, 
November 14th. 1894. 

8. Kwasnicki : Article published in the Przeglad Lekarski, October loth, 
1899. 

9. Scheube : Extracts from a work on tropical diseases. 

10. Bliekhahn: Med. News, December 9th, 1893, Philadelphia, Pa. 

11. Agnoli : " Consideraciones sobre dos casos de anemia por Ankylostoma 
Duodenal." La Cronica Medica, Lima, Peru, 1893, vol. x., p. 6. 

Fort Slocum, N. Y., March 23d, 1901. 

TRICHINOSIS. 

In March, 1896, a case of trichinosis entered Professor Osier's 
wards at the Johns Hopkins Hospital. The study of the blood of this 
case by Thomas K. Brown was the means of calling the attention of 
the profession for the first time to the value of blood examination 
in the diagnosis of trichinosis. The blood was examined daily for 
over two months. The total leucocyte count gradually rose from 
17,000 at entrance to 35,700 forty-four days later. Thence it de- 



TRICHINOSIS. 



435 



clined until, on the sixty-eighth clay, it was 11,000. The eosino-^ 
philes were 37 per cent (6, 300 absolute) at entrance, and rose with the 
total count until a percentage of 54 (19,500 absolute) was reached 
on the forty-fourth day (when the total leucocytes were 35,700). 
The highest percentage, 68.2, was reached on the forty-ninth clay, 
when the leucocytes were 17,700 (eosinophiles 11,070 absolute). 
On the sixty-eighth day (the date of discharge) the eosinophiles 
were 68 per cent (1,850 absolute). 

[For the daily counts of this sx^lendiclly studied case see p. 481.] 
A year later Brown studied a second case. His examinations 
showed as before a very marked eosinoi^hilia (see table LXIX.). 



Table LXIX.— Case II.— Blood Chart. 



Date. 


Leuco- 


Percentage of the Various 
Forms of Leucocytes. 


Total Number of Various 
Forms per c.mm. 


P. N. 
Neut. 


L. M. 

and T. 


s. 

Monos. 


Eos. 


P. N. 

Neut. 


s. 

Monos. 


L. M. 

and T. 


Eos. 


April 15th. . 


13,000 


43.1 


6.5 


1.4 


42.8 


5,600 


180 


840 


5,560 


16th.. 




47.7 


4.7 


4.5 


39.1 










17th. . 




52.0 


2.8 


7.6 


37.6 










18th. . 


8', 666 


















19th.. 




57.2 


2.8 


8.0 


32.0 










20th. . 


8", 666 


55.2 


3.8 


11.2 


31.8 


4,900 


1,000 


340 


2,830 


21st . . 


8.700 














22d. . . 


10,700 


58.0 


2.7 


11.7 


27.7 


6,200 


1,250 


290 


2,960 


23d. . . 


6,000 


56.2 


2.0 


15.2 


26.2 


3,370 


910 


120 


1,570 


24th. . 


11,000 


60.4 


4.0 


13.2 


22.4 


6,640 


1,450 


440 


2,460 


25th. . 


11.000 


57.2 


4.2 


18.6 


20.0 


6,290 


2,050 


460 


2,200 


26th.. 


9,600 


60.7 


5.3 


12.3 


21.7 


5,830 


1,180 


510 


2,080 


27th. . 


11,300 


63.0 


5.0 


17.0 


147 


7,120 


1,920 


560 


1,660 


28th. . 


12,700 


62.7 


40 


17.0 


16.3 


7,960 


2,160 


510 


2,070 


29th.. 


12,000 


67.0 


3.25 


15.25 


14.0 


8,040 


1,830 


390 


1,680 


May 1st . . 


10,700 


58.3 


4.0 


22.0 


15.7 


6,240 


2,350 


430 


1,680 


3d. . . 


13,000 


643 


4.0 


16,0 


15.7 


8,360 


2,080 


520 


2,040 


5th.. 


12,000 


647 


40 


16.0 


15.3 


7,760 


1,920 


480 


1,840 


7th. . 


9,300 


62.8 


40 


16.4 


16.8 


6,140 


1,530 


370 


1,560 


10th. . 


10,700 


60.4 


2.8 


16.4 


20.0 


6,460 


1,750 


300 


2,140 


12th. . 


11,000 


60.4 


3.3 


16.6 


19.6 


6,640 


1,820 


360 


2.160 


14th. . 


12,000 


58.8 


2.8 


18.8 


19.6 


7,060 


2,260 


340 


2,350 


17th.. 


9,000 


58.8 


3.6 


20.0 


17.6 


5,290 


1,800 


320 


1,580 



Brown's third case was studied in December, 1897. 

The blood (Table LXX.) on admission showed 45 per cent of 
eosinophiles, and this, as in the two previous cases, led to the diag- 
nosis of trichinosis and the subsequent confirmation of that diagnosis 
by the removal of a portion of muscle and the discovery of trichinae 
therein. 



436 SPECIAL PATHOLOGY OF THE BLOOD. 



Table LXX.— Case III.— Blood Chart. 



Date. 


Red blood 
corpuscles. 


Leuco- 
cytes. 


Per cent 
poh'niorpho- 

nuclear 
neutropbiles. 


Per cent 
large mono- 
nuclears and 
transitional. 


Per cent 
small mono- 
nuclears. 


Per cent 

eosino- 

philes. 


Dec. 22d . 






48.4 


4.7 


1.5 


45.4 


23d 




i7".o66 


52.7 


3.6 


3.1 


40.4 


27th . . 


4.700,000 


15,300 


42.4 


4.0 


5.6 


45.0 


Jan. 3d . , . 


4,300,000 


12,000 


42.2 


4.2 


4.6 


49.0 


7tb . . 




14.700 


31 '.6 


4.4 


19.0 


44.6 


lOth . . 


4,546,000 




32.4 


3.0 


21.8 


42.8 


14tli . . 




13.000 


35.2 


4.0 


23.4 


37.2 


22d . . . 




9.000 


45.5 


2.0 


17.7 


34.7 



This case was seen subsequently (July lOtli, 1898) six months 
after the disappearance of all symptoms, and the following {normal) 
count was registered. 

The count made on July 10th, 1898, was : 



Leucocytes (per c.mm.) 7.000 

Polymorphonuclear neutrophiles 68 per cent. 

Small mononuclears 23 

Large mononuclear and transitional forms 6 " 

Eosiuophiles 3 " 



A fourth case was reported by the same writer in January, 1899 
(Medical Xews). The counts were as follows: 



Date. 1898. 


Letico- 
cytes. 


Per cent 
polymorpho- 
nuclear 
neutropliiles. 


Per cent 
small mono- 
nuclears. 


Per cent 
large mononu- 
clears and 
transitlonals. 


Eosiuo- 
philes. 


August 8th 


18.100 










10th. 










48 


13th 


.... 


43" 


'7.3 


"i.7 


48 


28 th 


8.200 


45 


14.5 


2 


38.5 


September 4th . . . 


7.900 


49 


18.5 


2.5 


30 


18th. . . 




55.2 


19.6 


2 


23.2 


25th. . . 


' 9'. 666 


6L5 


16 


2.5 


20 


October 2d 


8,750 


54 


19.5 


2.5 


24 


November 5th. . . 




49 


40 


2.5 


8.5 


13th... 




64.5 


27 


3 


5.5 


20th.. . 




61 


27 


4.5 


7.5 



In January, 1900, Blumer^ and Xeumann report a "Family 
Outbreak of Trichinosis " including nine cases. The counts were as 
follows : 

^ American Jour. Med. Sciences. 



TRICHINOSIS. 



437 



Name. 


Date. 


Leuco- 
cytes. 


Per cent 
polynu- 
clears. 


Per cent 
transi- 
tionals and 

large mo- 
nonuclears. 


Per cent 
small 

mononu- 
clears. 


Per cent 
eosino- 
philes. 


■ - 

Case 1. D. V 


March 8th 


19,000 


47.4 


8.8 


3.2 


40.6 




13th 


18,000 












19th 


12,400 


50.6 


4.4 


7t6 


37.4 




26th 


20,600 


69.6 


5.6 


10.0 


14.8 




April 1st 


13,200 


73.0 


5.0 


12.0 


10.0 


Case 2. Mary C. . . . 


March otn 


8,400 


61.4 


6.8 


10.0 


21.8 


12th 


20,000 


51.6 


10.4 


14.6 


23.4 




19th 


17.200 


39,0 


4.8 


16.2 


40.0 




26th 


12.000 


48.0 


6.6 


14.6 


30.8 




April 1st 


16,000 


42.0 


4.3 


12.2 


41.5 


Case 3. A. V 


March 8th 


24,000 


56.8 


6.4 


3.6 


33.3 




12th 


14.000 


52.4 


3.8 


7.8 


36.0 




19th 


20,600 


64.4 


2.8 


5.2 


27.6 




26th 


18,000 


66.25 


4.0 


6.5 


23.25 




April 1st 


15,200 


56.6 


4.4 


10.4 


28.6 


Case 4. Mrs. D. V. 


March 8th 


8,000 


51.0 


7.8 


7.6 


33.6 




12th 




50.8 


4.2 


18.0 


27.0 




19th 


12,400 


50.6 


5.6 


11.0 


32.8 




26th 


13,200 


54.0 


5.0 


11.0 


30.0 


Case 5. T. V 


March 8th 


8,000 


32.6 


10.8 


6.4 


50.2 




12th 


14,000 


49.0 


4.2 


15.0 


31.8 




19th 


18,600 


41.4 


5.6 


10.8 


43.3 




26th 


14,600 


35.0 


3.5 


18.5 


43.0 


Case 6. R, G 


March 9th 


14,000 


45.6 


15.16 


7.0 


32.16 




19th 


17,200 


45.4 


2.6 


6.0 


46.0 




26th 


8,000 


48.8 


5.0 


10.8 


a5.4 




April 9th 


6,000 


64.4 


6.8 


12.3 


16.6 


Case 7. J. V 


March 12th 


16,000 


44.0 


9.2 


15.8 


31.0 




19th 


23,000 


53.2 


2.8 


6.3 


37.0 




26th 


16,600 


41.6 


6.0 


13.0 


39.4 




April 1st 


8,600 


39.3 


9.0 


16.1 


35.6 


Cases. R. V 


March 12th 


10,000 


39.0 


6.0 


20.0 


a5.o 




19th 


14,600 


36.0 


4.8 


8.5 


50.4 




26th 


12,600 


55.5 


5.5 


9.25 


39.75 




April 1st 


12,600 


44.0 


7.0 


5.5 


38.0 


Case 9. Mrs. R. G. 


March 9th 


12,400 


48.0 


9.6 


25.4 


17.0 




19th 


15,200 


59.2 


4.0 


16.8 


20.0 




26th 


12,600 


67.0 


6.5 


13.0 


13.5 




April 9th 


10,000 


74.0 


5.0 


13.0 


8.0 



My own experience is as follows : 



Case. 


Date. 


Red 
cells. 


White 
cells. 


Per cent 
haemoglobin. 


Per cent 
polynuclear. 


Per cent 
lymphocytes. 


Per cent 
eosinophiles. 


Per cent 
mast cells. 


Per cent 
myelocytes. 


1 


September 30th, 1897. 


5,120,000 
4,900,000 


11,000 
7,000 
1,410 
25,000 
23,000 
21,000 
11,000 
14,000 




39.0 


31.0 


28.0 


2.0 








36.5 
59 


46 


17 


.5 




3 


September 6th, 1899. . 

10th 

13th 




3 


34 


3 


3.0 
















15th, , 






71.2 


7 


19 




.8 




19th 














22d 



































438 



SPECIAL PATHOLOGY OF THE BLOOD. 



Date. 



September 29th 
November 4th.. 

10th. 

29th. 

First day 

Fourth day 

Seventh day... . 

Tenth day 

Thirteenth day. 
Fifteenth day.. 



Red 
cells. 



4,712,000 



5,728,000 



White 
cells. 



10,900 



15,601' 
11,600 
10,.500 
13,200 
16,100 
15,200 
17,900 



S2 



71.2 
53.6 
58.9 
67.8 

65 
60 
75 
39 
52 



9.6 

23 

32 

24.4 

11 

16 

18 

23 

13 

37 



Atkinson' reports one case as follows : 









c 


^1 




x 

*^ i 


Date. 


Red cells. 


White 
cells. 


Per cer 
aemoglo 


Per cei 
olynucU 


Per cei 
t^mphocj 


Per cer 
osinophi 










p. 




<u 


January 14th, 1899 








31.1 


9.5 


58.5 


18th 


5,528,bbb 


28,000 


93 


21.5 


24.2 


54.3 


25th 








25.6 


39.4 


35 


31st 








43.4 


16.6 


40 











Gwyn^ reports a similar case in which the eosinophiles ranged 
from 33 to 65.9 per cent during a period of six weeks. The leu- 
cocytes were at one time 17,000 per cubic millimetre. 

Stump^ found 52 per cent of eosinophiles in his case. 

W. W. Kerr* puts the following figures on record : 





Date. 
1899. 


Red cells. 


White 
cells. 


Per 
cent 
haemo- 
globin. 


Per 
cent 
polynu- 
clear. 


Per 
cent 
small 
lympho- 
cytes. 


Per 
cent 
large 
lympho- 
cytes. 


Per 
cent 
eosino- 
philes. 


Case 1 . . 


Nov. 9th 
10th 
11th 
13th 
15th 
16th 
17th 
18th 


5,800,000 
4,888,000 


25,000 
20,600 


85 


52.0 
49.4 
53.6 
41.7 
36.6 
35.0 
47.0 
46.5 


1.0 
3.6 
5.9 
4.3 
7.7 
5.3 
8.5 
10.5 


1.0 
2.8 
2.2 

3". 2 
7.6 
15.5 
10.9 


42.0 

44.2 - 

38.3 

54.0 

52.0 

52.5 

29.0 

31.1 












13,000 







1 Phila. Med. Journal, June 3d, 1899. 
^Centralbl. f. Bakt., vol. xxvi., Ko. ii. 
3 Phila. Med. Journ., June 17th, 1899. 
Phila. Med. Journal, August 25th, 1900. 



TRICHINOSIS. 



439 



Date. 
1899. 



Red cells. 



White 
cells. 



Per 
cent 
haemo- 
globin. 



Per 
cent 
polynu- 
clear. 



Per 
cent 
small 
lympho- 
cytes. 



Case 1. 



Case 2. 



Nov. 20tli 
22d 
23d 
27tli 
29th 

Dec. 3d 
8tli 
11th 
13th 

Nov. 17th 
18th 
20th 
- 21st 
22d 
23d 
24th 
25th 
27th 
29th 
1st 
2d 
3d 
5th 
6th 
8th 
9th 
11th 
13th 



Dec. 



4,250,000 



10,000 



100 



3,340,000 



20,000 



3,300,000 



17,000 



48 


0 


50 


8 


52 


4 


40 


0 


22 


5 


28 


7 


10 


6 


23 


6 


23 


9 


41 


6 


53 


2 


37 


0 


34 


0 


20 


0 


15 


3 


10 


4 


10 


5 


17 


0 


6 


5 


4 


2 


11 


4 


40 


0 


14 


8 


0 


75 


3 


1 


10 


9 

2 


11 


13 


1 



8.0 
2.0 
10.9 
15.0 
19.8 
2.8 
6.0 
13.2 
9.8 

16.4 
18.9 
11.0 
11.0 
8.2 
5.7 
7.2 
6.4 
6.4 
3.9 
3.0 
10.1 
7.3 
8.0 
5.0 
9.5 
3.6 
18.2 
9.4 



Harlow Brooks^ examined. the, blood in one case, and found 
at the time of admission to the Bellevue Hospital (February 2d, 
1900) 18,000 leucocytes, with 10 per cent of eosinophiles ; on 
February 12th, 1900, 44 per cent of eosinophiles ; thence a steady 
increase up to 83 per cent, followed by a decline, until on March 
14th 15 per cent of eosinophiles was present. Many of the granules 
wer smaller than those of normal eosinophiles, but there was no evi- 
dence of forms transitional between eosinophiles and neutrophiles. 

F. P. Kinnicutt^ reported a similar case, and H. C. Gordinier^ 
mentions two, one presenting 77 per cent, the other 29.9 per cent 
of eosinophiles. 

' Med. Record, May 19th, 1900. - - - 

2 pi-actitioners' Soc, February 2d, 1900. 

3 Medical Record, October 20th. 1900. ' 



440 



SPECIAL PATHOLOGY OF THE BLOOD. 



Su7nmary. 

From the total of counts in cases here assembled the constant 
presence of eosinophilia in trichinosis may safely be inferred. 

Diagnostic Value. 

The characteristic blood lesions change trichinosis from the 
position of a disease very difficult and uncertain of diagnosis (with- 
out excision of a bit of muscle) to one whose recognition is usually 
easy. Cases formerly diagnosed as typhoid, muscular rheumatism, 
or neuritis now find their true interpretation. 

Other Intestinal Wo7'ms. 

Bucklers, working under Leichtenstern's direction, has recorded 
the following data in cases affected with various more or less inof- 
fensive worms : 

I. Anguillula Intestinalis. 



Per cent. 

Eosinophiles 13.5 

Polynuclears 38.5 

Lymphocytes and transitional 48 

II, Anguillula Intestinalis with Ankylostoma. 

Per cent. 

Eosinophiles 15 

Polynuclears 58 

Lymphocytes and transitionals ^ 27 

III. 





Case I. 

Oxyuris and 
ascarides. 


Case II, 
Oxyuris. 


Case III. 

Oxyuris with 
ascarides and 
trichocephalus. 


Case IV. 

Oxyuris with 
ascarides, trich- 

ocephalus and 
Taenia saginata 


Eosinophiles 

Lymphocytes and tran- 
sitionals 


19 per ct. 
53 " 

28 " 


16 per ct. 
63 " 

21 " 


8 per ct. 
69 " 

23 " 


5.7 per ct. 
63.3 " 

31.0 " 


IV. Ascamdes (alone). 




Case I. 


Case II, 


Case III. 


Case IV. 


Eosinophiles 

Lymphocytes and tran- 


7.4 per ct. 
55.0 " 

37.6 " 


8.5 per ct. 
55.0 " 

26.5 " 


9.8 per ct. 
50.0 " 

40.2 " 


1.8 per ct. 



TRICHINOSIS. 



441 



The report of the Jenner Hospital at Berne (1890) includes the 
account of a case in which ascaris was present in large numbers. 
The blood showed but 2,480,000 red cells before the expulsion 
of the parasite by santonin; two weeks later the red cells were 
4,200,000. 

V. T^NiA (Bucklers). 





Case I. 


Case II. 


Case III. 


Case IV. 


Case V. 




Taenia 


Taenia 


Taenia 


Taenia 


Taenia 




Solium. 


Saginata. 


Nana. 


Saginata. 


Saginata. 


Eosinophiles 


8.2 p. ct. 


5.5 p. ct. 


7.0 p. Ct. 


5.0 p. Ct. 


10.0 p. Ct. 




49.4 " 


65.0 " 


42.0 " 






Lj-mphocytes and 












transitionals 


42.4 " 


29.5 " 


51.0 " 







CHAPTER XIII. 



DISEASES OF THE SKIN. 

DERMATITIS. HERPETIFORMIS. 

According to Leredde, who has written extensively on the con- 
dition of the blood in this disease, the following terms are in use to 
designate the same actual set of facts : Dermatitis herpetiformis ; 
Dtihring's dermatosis; Polymorphous pruriginous dermatitis; 
Hydroa (Unna) ; Pemphigus vegetans (Neumann); Hallopeau's 
infectious dermatosis ; Herpes gestationis. 

In all of this he finds marked constant eosinophilia, averaging 
16 per cent. At times the percentages may reach 25 or 30. 

My own experience includes three cases, one diagnosed as der- 
matitis herpetiformis, the others as hydroa sestivale. The coimts 
were as follows : 





Case I. 
Dermatitis herpe- 
tiformis. 


Case II. 
Hydroa asstivale. 


Case III. 
Hydroa sestivale. 


Polynuclear neutrophiles . . 


47 per cent 


40.0 per cent 


34 per cent 




25 " " 


42.4 " " 


43 " " 




8 " " 


8.6 " " 


8 " " 


Eosinopliiles 


19 " " 


8.2 " " 


15 " " 


Myelocytes 


1 







Brown' reports the following figures in a case of dermatitis 
herpetiformis (twenty-seven years' duration) : 





June mh, 
1899. 


June 17th, 
1899. 


June 25th, 
1899. 


June 30th, 
1899. 


Sept. 5th, 
1899. 




5,128,000 
14,000 






5,163,000 
9,000 


5,808,000 
9.700 


White cells 














Per cent. 
32.8 
38.0 
29.2 


Per cent. 
31.3 
24.4 
44.3(!) 


Per cent. 
29.25 
34.5 
36.25 


Per cent. 
39.25 
21.5 
39.25 


Per cent. 
36.0 
34.4 
29.3 



' Soc. for Original Research, Conn., October 12th, 1899. 



PSORIASIS. 

Erythema. 



443 



Age. 



29 



27 



18 
17 
24 



Red cells. 



White 
cells. 



19,700 

20,400 
12,900 
18,400 
6,800 

llAOO 
8,200 
6,150 



Per cent 
haBino- 
globln. 



65 



Remarks. 



First day. Temperature 102°; ery- 
thema nodosum and multiforme. 
Second day. Temperature 103°. 
Sixth day. Temperature 98°. 
Temperature 104°. 

Temperature 104°, third day. Eosino- 

philes not 

Nodosum. 
Temperature 102°. 

Dilf. 425 cells. Polynuclear, 69; lym- 
phocytes, 30; eosinophiles, 1. 



HERPES TONSURANS. 



Mark A. Brown' records this blood count: White cells, 10,700; 
of these, there were eosinophiles,_25,.2 per cent ; p.olyjiuclears, 45.6 
per cent; lymphocytes, 29.2 per cent. 



CHRONIC ECZEMA. 

Thomas R. Brown^ reports a case of chronic eczema, studied 
at the Johns Hopkins Hospital, in which three counts showed 22.6 
per cent, 24 per cent, and 22. 7 per cent, of eosinophiles. 

Zappert (loc. cit.) notes a similar case with 8,600 leucocytes per 
cubic millimetre, 9.9 per cent of which were eosinophiles (843 abso- 
lute). Bettmann records 45 per cent eosinophiles in a similar case. 

SCLERODERMA. 

Two cases in Zappert' s series showed: 

Per cent 

Leucocytes. eosinophiles. 

1 16,690 9.4 (1,580 absolute) 

2 9 000 7.7 ( 694 " ) 

PSORIASIS. 

One of Zappert' s cases had 8,600 leucocytes, with 9.8 per cent 
of eosinophiles (850 absolute). 

^ In Conn. Lancet-Clinic, December 22d, 1900. 
2 Jour, of Exp. Med., vol. iii., p. 320. 



444 SPECIAL PATHOLOGY OF THE BLOOD. 

PEMPHIGUS. 



Zappert's three cases showed: 



Cases. 


Red cells. 


White cells. 


Per cent eosinophiles. 


1 


3,952,000 
3,940,000 
4,120,000 


5,300 
10,600 
1,640 


33.0 (1,750 absolute). 

14.1 (1,500 absolute). 

29.2 (4,800 absolute). 


2 


3 




LUPUS. 

Two cases (Zappert). 


Cases. 


Red cells. 


White cells. 


Per cent eosinophiles. 


1 


3,224,000 
4,250,000 


9,200 
9,450 


12.2 (1,126 absolute). 
7.3 ( 696 absolute). 


2 





CHAPTER XIV. 



THE BLOOD IK INFANCY. 

I. All the signs by tvhich sickness is shown in the blood of adults 
are exaggerated in children. Their blood is apparently more sensi- 
tive to the action of any morbid influence. Causes leading to but 
slight anaemia or leucocytosis in the adult, produce grave anaemia 
and very marked leucocytosis in children. Into the reasons for this 
I shall not attempt to enter. The increased toxicity of their serum 
compared to that of adults, and the relatively recent establishment 
of the functions for producing and destroying blood have been sug- 
gested as explanation. 

Comparatively slight hemorrhages, gastro-intestinal or respira- 
tory disorders, which would not impoverish an adult's blood may 
produce considerable anaemia in a young child. 

II. All forms of anaemia in infancy are apt to be associated with 
enlarged spleen. 

III. I have already alluded to the polycythaemia and leucocyto- 
sis of the new-born, and the gradual fading out of these relative 
abnormalities as the child grows up. In judgments as to the pres- 
ence or absence of leucocytosis in infancy, these physiological varia- 
tions are too often lost sight of, especially as the proper leucocyte 
count for any given infant depends not simply on its age but on the 
backwardness or forwardness of its development. As with the fon- 
tanelles, the growth of the blood toward adult conditions may be 
retarded by congenital weakness (infantile atrophy, marasmus) or 
inherited disease (tuberculosis, syphilis), as well as by acquired 
sickness (rickets, cholera infantum). 

Under the influence of any of these drawbacks a sick child's 
blood may be no further developed at three years than that of a 
healthy child of eighteen months. 

IV. When we remember that in early infancy the leucocytes 
differ from those of adults not only in number but in that the lym- 
phocytes are relatively more numerous (" lymphocytosis of infancy "), 
we shall understand that any influence like rickets or syphilis, which 



446 



SPECIAL PATHOLOGY OF THE BLOOD. 



retards development, will show lymphocytosis together with the 
increased leucocyte count. Qualitatively as well as quantitatively 
the blood reverts to a more infantile condition. 

y. This shows itself not merely in the leucocytes but in the red 
corpuscles. During the first days after birth the infant's blood 
shows greater variations m size and shape than that of adults, as 
if the type were not yet quite fixed. The majority of authors also 
find a few normoblasts in the first few days of life. These are not 
invariably present, doubtless because in some children the blood at 
the time of birth is more developed than in others. 

Under pathological conditions the red cells revert to this, earlier 
type, and deformed or nucleated corpuscles are plentiful. This is 
more marked than in anaemia of the same grade occurring in adults. 
An ansemia that shows but thirty nucleated erythrocytes per cubic 
millimetre in an adult might show ten times that number in a child. 

VI. As I said before, all blood changes are exaggerated in in- 
fancy. This includes such physiological changes as the digestion 
leucocytosis or that following cold bathing as well as pathological 
leucocytosis and ansemia, and changes in the degree of dilution or 
concentration of the blood seem to be similarly exaggerated, as is 
seen, e.rj., in the physiological variations in the specific gravity of 
the serum (Hock and Schlesinger'). 

VII. The hoimoglohin, though relatively high at birth and for 
the first few weeks, is lower than that of adults during the rest of 
childhood. The high percentages of the earliest weeks are not due 
to a polycythsemia, but to a genuine increase of hsemoglobm in the 
individual cells (Schiff ^), color indexes being often over 1. 

It is indispensable, therefore, that we should know the age and 
degree of development of a child before we can draw accurate mf er- 
ences from its blood. In many of the cases reported in literature 
we are unable to judge whether the blood condition is pathological 
or not, because the age of the child is not given. For example, v. 
Limbeck ^ notes a case of acute gastritis reported by Fischl ^ as hav- 
ing an unusually high percentage of lymphocytes (59.4 per cent). 
But this is physiological in the first days of life, and may have been 
so in this case, the age not being given. 

iHock and Schlesinger: Centralbl. f. klin. 3Ied., 1891. 
2Schiff : Zeit. f. Heilk., vol. xi., 1890. 
^v. Limbeck: loc. cit., p. 373. 
^Fischl: Zeit. f. Heilkunde, 1893. 



THE ANEMIAS OF INFANCY. 



447 



Observations of this sort should always represent a comparison 
between the conditions present before and during the sickness in 
question. 

Bearing these general considerations in mind, we shall be better 
able to find our way among the complications and perplexities of 
the blood conditions in infancy. 



As above mentioned, anaemic infants are apt to have enlarged 
spleens. This may be due either to the anaemia or to some disease 
accompanying or underlying the anaemia {e.g., rickets, syphilis). 
It seems more probable that the hypertrophy is not directly or ex- 
clusively dependent on the anaemia, inasmuch as similar blood 
changes are found without splenic enlargement. By far the greater 
number of reported cases of severe infantile anaemia are accompanied 
or caused by such diseases as rickets and hereditary syphilis, both 
of which may cause splenic hyperplasia even when no anaemia is 
present. It seems probable that the anaemia and the enlargement 
of the spleen are alike symptomatic of an underlying disorder. 

1. Some writers {e.g., Luzet') divide the anaemias of infancy 
into two classes : those with splenic enlargement and those without 
it. Luzet considers that the former class is severer than the latter 
and more apt to show large numbers . of nucleated red corpuscles 
than those with normal-sized spleens. This classification, however, 
does not always hold. We may have very severe anaemia without 
splenic enlargement and splenic enlargement with slight anaemia, 
and the presence or absence of numerous nucleated red corpuscles 
is governed by conditions other than the size of the spleen. 

2. Another classification of children's anaemias was proposed 
in 1892 by Monti and Berggrim ( " Die chronische Anamie im Kin- 
desalter," Leipzig, 1892) . They divided the cases into the mild and 
the grave, each group being subdivided into those with leucocytosis 
and those without it. 



They rightly discard the term "splenic anaemia," corresponding 
as it does to no single set of blood changes. The above classifica- 
' Luzet: Diss., Paris, 189L 



THE ANEMIAS OF INFANCY. 



Secondary anaemia of infancy = 



fMild 



_ ^ With leucocytosis. 
~ ( Witliout leucocytosis. 




448 



SPECIAL PATHOLOGY OF THE BLOOD. 



tion puts j^ernicious anaemia, leukaemia, and ansemia infantum pseu- 
doleukaemica (y. Jaksch) in a different category. 

(a) Mild cases of secondary anaemia show no deformities in the 
shape or size of the red cells. The color index may or may not be 
lo^y. The cases with leucocytosis are much more numerous than 
those without it and more apt to have a low color index ; in other 
words, the loss of corpuscle substance is greater and the cases are 
approaching the imaginary boundary between "mild "and "grave." 

(b) The grave cases have ^^oikilocytosis, and of course a greater 
reduction of corpuscle substance. 

" Chlorotic " conditions, and most but not all those with enlarged 
spleen, come under this heading ; also most of those due to heredi- 
tary syphilis, ]Drolonged diarrhoea, and rickets. 

In 1894 Monti ' gave the following classified lists of the com- 
monest antecedents of secondary anaemia in infancy : 



He points out that cases with leucocj-tosis are usually graver 
than those without it and may develop into pernicious anaemia ; also 
that the presence of leucoc}i:osis does not X)oint to malignant disease, 
suppuration, or any of the causes which usually account for it m 
adults. 

Grave cases with leucocj-tosis in infants under twelve months 
are apt to develop:) into the anaemia infantum pseudoleukaemica, or 
into true leukaemia or pernicious anaemia. 

On the whole, the division of Monti and Berggrtin seems much 
better than that according to the particular causes, e.(/., "rachitic 
anaemia," "syphilitic anaemia," etc., for there is no particular set 




- In the ID other during pregnancy. 



2. Acquired . . - 



^ 2. Other causes. <| 



1. Hemorrhage. < 



f From navel. 
I After circumcision. 

'l Scurvy, purpura, hamophilia, Werlhof s 
1^ disease, melana. 
"Inanition. 

Bad hygiene (lack of Hght, air, etc.) 
Post-febrile. 

Xephritis, diarrhoea, serous effusions. 
<| Svphilis. 
Eickets. 
Suppuration. 

Diseases of liver, spleen, bone, or lymph 
t glands. 



1 Wiener med. Woch., 1894. 



THE ANEMIAS OF INFANCY. 



449 



of blood changes that follows rickets, syphilis, or any other disease. 
In connection with various diseases of infancy, and particularly 
Avith those last named, we may have anaemia of any grade of sever- 
ity, from that reducing the red cells to 4,000,000 down to cases with 
only 500,000 red cells per cubic millimetre or even less. The worse 
the case is the more likely is it to be accompanied by leucocytosis 
and the more numerous will be the nucleated red corpuscles, always 
more numerous here than in anaemia of adults. 

In sijphilis, hereditary or acquired, the red cells may fall below 
1,000,000 and the leucocytes may rise as high as 58,000 (Loos). 
The hsemoglobin may be proportionally diminished, or may be even 
lower than the percentage of red cells, so that a " chlorotic " condi- 
tion obtains. 

Such cases have been called chlorosis, but it seems better to con- 
fine this term to anaemia of unknown origin and favorable course 
occurring in women soon after puberty, since obviously secondary 
cases may have similar blood. 

Rickets in a case observed by v. Jaksch caused a fall of the 
red cells to 750,000, and Luzet counted 1,590,000 in a similar case. 
The haemoglobin is usually low, but Hock and Schlesinger found 
60 per cent with 2,300,000 red cells, a color index of 1.2 -f . 

Leucocytosis may occur even when no anaemia is present. Hock 
and Schlesinger found 45,000 leucocytes in a rachitic child of six 
teen months, sound in other respects and not anaemic. .Acute gas- 
tritis causes at first only leucocytosis (with increased percentage of 
lymphocytes). If it becomes chronic the reduction of red cells is 
severe. Hayem found only 685,000 red cells per cubic millimetre 
in an infant of two months, though recovery eventually took place. 

In tuheixulosis of the lungs and peritoneum in a child of seven, 
Monti and Berggrlin counted 3,230,000 red and 17,200 white cells 
with 52 per cent of haemoglobin. 

Qualitative Changes. 

The exaggeration characteristic of all blood changes in infancy 
extends to the presence of nucleated red corpuscles, which in all 
forms of severe anaemia are very numerous. What has been de- 
scribed above (page 91) as the typical megaloblast, a large pale- 
stained nucleus in a very large cell (see Plate IV.), is relatively 
rare in infancy. The nuclei are almost always deeply stained what- 
ever their size, and apt to be small. Dividing nuclei are very com- 
29 



450 



SPECIAL PATHOLOGY OF THE BLOOD. 



mon, both by karyolysis and karyokinesis. These changes are most 
often found in the anaemias of the severest type and those which 
resemble leukaemia (see below, page 456), but may occur in any 
marked secondary anaemia. Polychromatophilic and " degenera- 
tive " changes are very common in severe cases. 

The increased leucocyte count, so frequently found, is often 
made up of a majority of lymphocytes. This change, as above said, 
is not characteristic of rickets, syphilis, or any other cause of anae- 
mia, but it is to be regarded as a mark of the arrest of develoj^ment 
or reversion to an earlier type of tissues brought about by various 
diseases iii early infancy. Sometimes the large lymphocytes and 
sometimes the small are in excess. 

A further qualitative change already alluded to (see above, page 
118) is the occurrence of myelocytes. We have seen that small per- 
centages of these cells are not uncommonly seen in the anaemias of 
adults. Now this, like all other blood changes, is exaggerated in 
infancy. Myelocytes are more apt to appear and in greater numbers. 
Their presence is not characteristic of any one disease, but they are 
commonest in the severer types of secondary anaemia, such as those 
following syphilis and rickets. Their significance is about the same 
as that of normoblasts. At times, however, they are so namerous 
as to make us hesitate somewhat before we exclude splenic-myelo- 
genous leukaemia. 

This brings us naturally to the, discussion of the difficulty of 
distinguishing the different blood diseases in infancy, which naturally 
centres in the question of the existence and nature of the so-called 

"ANEMIA INFANTUM PSEUDOLEUK^MICA." 

Von Jaksch's' description of this disease (which he was the first 
to recognize) includes the following elements : 

1. Grave anaemia — e.g., 820,000 red cells per cubic millimetre 
in one case. 

2. Extensive leucocytosis — e.g., 54,660 white cells per cubic 
millimetre, in the same case. 

3. Great variations in the form, size, and staining of the white 
cells. 

4. Deformed, degenerated, and nucleated red cells. 

Von Jaksch admits that none of these blood changes is charac- 

iVou Jaksch: Wien. khn. Woch., 1889, Nos. 22, 23. 



AX.EMIA INFANTUM PSEUD0LEUK.5:MICA. 



451 



teristie of the disease, but thinks that its title to the position of a 
distinct and separate disease rests upon dinir'd data, the more im- 
portant of which are : (1) A great enlargement of the spleen with- 
out any such accompanying enlargement of the Jicer as is usually 
found in leukaemia (the lymph glands are sometimes enlarged). (2) 
A relatively good j^rognosis. (3) Post mortem we find no positive 
evidence of leukaemia. 

This description was given by v. Jaksch ' in 1889. He stated 
the relation of white to red corpuscles as 1 : 12, 1 : 17, and 1 : 20 in 
the cases seen by him. Later he reported three cases in one of 
which the white cells numbered 114,150, and the red 1,380,000. 
The differential counts are not carefully given. 

Almost at the same time Hayem" reported a similar case, and 
noted the abundance of nucleated red corpuscles many of which 
were undergoing mitosis. This was verified by Luzet ^ in May, 
1891 (Arch. gen. de Jled.), who reported two cases. His descrip- 
tion of the disease differs considerably from that of v. Jaksch. He 
finds no greater difference between liver and spleen than often exists 
in true leukaemia. The course of the disease, though sometimes 
chronic, usually ends in death. The leucocytosis in Luzet" s cases 
was less marked than in those of v. Jaksch and not greater than 
that occurring in many anaemias of children. He dwells particu- 
larly on the large number of nucleated red cells, and the fr':'<i iiency 
of mitosis, and considers fliis the most important diagnostic pomt. 

Although Luzet continues to use the name suggested by v. 
Jaksch, he describes the disease so differently that it is difficult to 
see why the same title should be given to it. He agrees with v. 
Jaksch in thinking that it is not simply a severe secondary anaemia 
due to syphilis, rickets, tuberculosis, or infectious disease. 

Somewhat similar cases had already been described by various 
Italian writers {e.g., Fede) imcler the title of Infurtb-^^ Sj^^dynir 
A71 rem in of In fa n ts . " 

Among others who have written on the subject are Baginsky.^ 
Senator,' Fischl,® Andeoud,' Monti and Berggrtin,- Felsenthal," 

1 Yon Jaksch : Wien. kliu. Woch., 1889, Xos. 22, 23. 
2Hayem: Gaz. des Hopitaux. 1889, Xo. 30. 
3 Luzet: Diss., Paris. 1891. 

•^Baglnsky: Arch. f. Kinderlieilk. , 1892, vol. xiii. 

^Senator: Berlin, klin. Woch., 1892. •^Fisclil: loc. cit. 

■'Andeoud: Rev. med. de la Suisse rom., 1891, p. 507. 

® Monti and Berggrlin : loc. cit. ^ Felsenthal : he. cit. 



452 



SPECIAL PATHOLOGY OF THE BLOOD. 



Eauduitz,' Epstein/ Alt and- Weiss/ Hock and Sclilesinger/ 
Crocq," and Eotch/ 

The majority of these writers report very little as to the differ- 
ential counts of white corpuscles. An increased percentage of the 
polymorphonuclear forms is mentioned by man}^, but Eotch in a case 
Avith 1,311,250 red cells and 116,500 white cells found only 16 per 
cent of the polymorphonuclear variety with 46 per cent of small 
lymphocytes, 34 per cent of large lymphocytes, and 4 per cent 
eosinophiles. A second case had only 14 per cent of polymorpho- 
nuclear cells and 84 per cent of lymphocytes (large and small). 

Yon Jaksch noted the lack of any relative increase of eosino- 
philes, supposing this to be a means of distinguishing his cases from 
true leukaemia. Luzet, on the other hand, found eosinophiles nu- 
merous. (This of course has no weight for or against leuksemia.) 

Klein {loc. cit.) noted the occurrence of myelocytes in small 
number. 

The discrepancy of these different reports is suggestive. 

The chief importance of the heterogeneous group of cases which 
have received the name of ancemia infantum j^jseudoleukcemiexi seems 
to me to be as a proof of the difficulty of distinguishing the various 
blood diseases in infancy. 

Among the cases reported under this name are some which 
might be any one of the following list : Pernicious anaemia, second- 
ary anaemia with leucocytosis, Hodgkin's disease, lymphatic leukae- 
mia, and probably splenic-myelogenous leukaemia. 

(r^) Most of the fcAv reported cases of pernicious anaemia in 
infancy have shown moderate leucocytosis (as compared with adult 
blood), a fact which deprives us of one of the means of distinguish- 
ing the disease from secondary anaemia. The reports as to nucleated 
corpuscles very rarely separate normoblasts from megaloblasts, and 
we have no way, therefore, of being sure on this important point. 
The high color index and large diameter of the red cells are occa- 
sionally seen in other anaemias of infancy and are not always present 
in pernicious cases. The great fatality of all kinds of anaemia in 

iRaudnitz: Prag, med. Wocb., 1894, p. 6. 

"2 Epstein: Prag. med. Wocli., 1894, p. 6. 

^ Alt and Weiss : Centralb. f. med. Wissenschaf t. , 1892. 

^ Hock and Schlesinger: loc. dt. 

^Crocq: "Etude sur I'Adenie," etc., Brussels, 1819 (Lamartin). 
«Rotcli: Paediatrics, 1895, p. 361. 



ANEMIA INFANTUM PSEUDOLEUK.-EMICA. 



453 



infancy prevents our calling a G?ise pei'^f ^cious because of a fatal ter- 
mination. Enlargements of tlie liver and spleen occur in many cases 
of each type of infantile anaemia, and occasionally in pernicious 
anaemia of adults. They do not, therefore, exclude pernicious anae- 
mia in infancy. 

Bearing these facts in mind, it is evident that some of Luzet's 
cases of anaemia infantum pseudoleukaemica " may have been per- 
nicious anaemia. Von Jaksch's own cases may have been either ((/) 
Hodgkin's disease with leucocytosis, (b) grave secondary anaemia 
with leucocytosis (Monti and Berggrim), or (c) leukaemia. 

(a) Hodgkin's disease, which v. Limbeck finds to be very com- 
mon in infancy, may affect the liver and spleen and not the exter- 
nal lymph glands, and may be accompanied by anaemia and leuco- 
cytosis such as V. Jaksch describes. Epstein considers that this is 
the case, and denies the existence of any such disease as the anaemia 
infantum pseudoleukaeniica. 

(h) As any anaemia secondary to rickets or syphilis may have 
enlarged spleen and liver and marked leucocj-tosis, we cannot tell 
from V. Jaksch's description that we are not dealing in his cases 
with secondary anaemia. 

(c) Since v. Jaksch does not give any accurate differential count 
of the leucocytes, there may have been large numbers of myelocytes 
in his cases for all we know, or an overwhelming percentage of 
lymphocytes, i.e., either type of leukaemia. 

One of the cases reported by Eotch as "anaemia infantum 
pseudoleukaeniica " had 80 per cent of lymphocytes in a leucocyte 
count of 116,500, the ratio of white to red cells being 1 : 11, and the 
nucleated corpuscles abundant. The external lymph glands as 
well as the liver and spleen were enlarged. How such a case is to 
be distinguished from lymphatic leukaemia without autopsy I cannot 
see. Large numbers of nucleated corpuscles with mitoses (present 
in this case) are to be found in any anaemia of infancy in which the 
red cells, as in this case, have sunk as low as 1,311,500, and there- 
fore do not exclude leukaemia. 

Yon Jaksch protests that his cases are not secondary to rickets 
or any other disease, but Fischl ' in a careful study of all the pub- 
lished cases finds that, out of a total of eighteen cases, sixteen had 
severe rickets and two hereditary syphilis. 

The writings of Eaudnitz, Ebstein, Felsenthal, Fischl, and v. 
1 Fischl: Zeit. f. Heilkunde, 1892. 



454 



SPECIAL PATHOLOGY OF THE BLOOD. 



Limbeck, wliicli deny the separate existence of the anaemia infan- 
tum pseudoleukaeniica, are convincing to me, and are reinforced by 
the few cases of bad anaemia in children which I have seen. We 
must distribute the cases of anaemia with leucocytosis and large 
spleen under pernicious anaemia, secondary anaemia, and leukaemia. 

. But our problem is not yet nearly solved. All we have gained 
is the belief that v. Jaksch's new disease does of help us to classify 
these doubtful cases. The difficulty is still very great. The fol- 
lowing cases reported by Dr. Yickery in the Mediad Xeirs for De- 
cember, 1897, illustrate this: 

Case L — A male child of sixteen months with symptoms of 
grave anaemia, greatly enlarged spleen and slightly enlarged liver, 
showed the following figures: Eed cells, 2,500,000; white cells, 
22,000. Differential count of 500 cells showed : Lymphoc;>i:es, 53.8 
per cent (46.2 of the smaller type) ; polymorphonuclear cells, 29.4 
per cent; eosinophiles, 6.2 per cent; myelocj'tes, 10 per cent. 

While counting these, 147 nucleated red corpuscles were seen, of 
which 21 were normoblasts, 50 megaloblasts, and 47 microblasts ; 
6 showed mitosis in their nuclei. 

The child died shortly after without any complication or inter- 
current disease, ^^"o autopsy. No evidence of rickets or sj'philis 
or other previous disease. 

Case II. — Young infant with enlarged external lymph glands 
and very large spleen. July 14th, 1897— Eed cells, 4,300,000; 
white cells, 31,000; haemoglobin, 60 per cent; polymorphonuclear 
neutrophiles, 57.5 per cent; small lymphocytes, 26 per cent; large 
lymphocytes, 15 per cent; eosinophiles, 0.5 per cent; myelocytes, 
1 per cent. 

One or two nucleated red corpuscles in every field. Out of 100 
of them 89 were large and 11 small. Many showed mitosis.. Pol}^- 
chromatophilic forms numerous. July 19th — Seventeen megalo- 
blasts seen while counting 1,000 white cells. Blood is otherwise 
about the same. The case. was lost sight of and not traced. 

Now I see no reason for supposing these cases to represent a new 
type of disease, and yet I cannot feel 23erfectly safe in classifying 
them as primary anaemia, secondary anaemia, or leukaemia. 

{(() Primary or pernicious anaemia should have a lower count of 
red cells. The percentage of myelocytes in the first case (10 per 
cent) is higher than in au}^ other case of pernicious anaemia on 
record, though in one adult case with autopsy I found 9.2 per cent 
with a leucocytosis of 12,500, or 1,150 myelocytes per cubic milli- 
metre, against 2,200 per cubic millimetre in this case. 

(h) It is hard to call an anasmia secondary which kills with no 



ANEMIA INFANTUM PSEUDOLEUK^MICA. 



455 



complications and when there is no evidence of any disease to which 
it can be secondary. 

(c) For splenic myelogenous leukaemia the total leucocyte count 
and the percentage of myelocytes are very small in either case. 
Still the leucocyte count may drop very low in leukaemia even with- 
out any inflammatory complication. Such a case is reported by 
Osier, in which the leucocytes fell to 7,500, of which only 300, or 
four per cent, were myelocytes. 

Hayem {loc. clt., page 864) in a ten-months old child counted 
2,712,500 red and 33,000 white cells, almost the same figures as in 
the case just quoted. [Hayem unfortunately gives no differential 
count, but apparently considers the case leuksemic because of the 
enormous number of nucleated red cells, many with mitoses.] 

Morse's case of leukaemia in infancy had 2,900,000 red and 
48,000 white cells. Twenty-one and four-tenths per cent of the 
leucocytes, or about 10,000, were myelocytes. The same abun- 
dance of nucleated red cells (some with mitoses) were here present 
as in Hayem' s case, so that there is evidently nothing peculiar in 
their presence in the disease described by v. Jaksch, as Luzet sup- 
posed. 

These cases show that leukaemia may at certain periods present 
just such a blood picture as was present in the above-quoted case, 
and that the number of leucocytes in the leukaemia of infants may 
be no greater than that in any anaemia with the leucocytosis so com- 
mon in children. 

It seems to me the most natural conclusion to be deduced from 
these facts is that we meet with cases in infancy luhich are apjjav- 
ently intermediate between leukcemia and j^e^mic ions anmniia. I have 
pointed out elsewhere that there are many pomts of resemblance 
between the two diseases. The case of leukaemia reported by Osier 
showed at one period — the period of remission — a fall in the num- 
ber of leucocytes and in the percentage of myelocytes till the blood 
was practically that of pernicious anaemia. 

Dr. Rotch's case (above quoted) is another in which the diagno- 
sis seems to lie somewhere intermediate between the two diseases, 
anaemia and leukaemia. 

The case which I have quoted above seems to me on the whole 
nearer to the type of pernicious anaemia than of leukaemia, and Dr. 
notch's nearer to the latter than to the former; but each is really 
intermediate, so far as the blood fjoes, between the two diseases. I 



456 



SPECIAL PATHOLOGY OF THE BLOOD. 



have no intention of suggesting tliat the organic lesions in these 
cases are intermediate between leukaemia and pernicious anaemia. 
It is simply the blood that is so. 

Engel's case, reported in Virchow's Arcliiv, vol. 135, suggests 
the same thing. He calls the case one of ^^pseudo-pernicious ancH- 
miaJ' Myelocytes were abundant. 

Polymorjjhous Condition. 

This illustrates that " polymorphous " condition of the blood 
which V. Jaksch supposed to be characteristic of the anaemia infan- 
tum pseudoleukaemica. The same thing was very marked in all the 
bad cases of anaemia which I have seen, including the case above 
mentioned, and a case of true leukaemia in a girl of eight. The im- 
pression one gets from the field of a stained specimen is that no two 
white corpuscles are oliJce. Every species is subdivided into several 
sub-varieties and all stages of degeneration are to be seen in each 
variety. But this is characteristic of any very severe infantile anae- 
mia and not of any single type. 

LEUKEMIA. 

In Morse's careful article of August, 1894 {Boston Med. and 
Sury. Journal), twenty cases of leukaemia in infancy are collected. 
As he rightly says, probably most of these cases were not genuine. 
Only one of them includes a differential count, and this is in a lym- 
phatic case. Morse's is the only one of the splenic-myelogenous 
type on record in which the diagnosis is made reasonably certain by 
a color analysis. Fischl in 1892 said that there was no case on 
record with a differential count. 

A case was seen in 1890 by Dr. F. C. Shattuck, which was ap- 
parently acute, the symptoms appearing only six weeks before 
death. Cover-glass preparations examined by W. S. Thayer showed 
a ratio of about 1 white to 20 red cells. The differential count ^ 
showed: Small lymphocytes, 97.9 per cent; large lymphocytes, .7 
per cent; polynuclear cells, 1.4 per cent; eosinophiles, .08 per cent. 

The other case reported by Morse has been mentioned above. 

Charon and Giratea^ have recently reported a case in a child of 

' Reported by Thayer in the Boston Medical and Sm'gical Journal, 1893, 
vol. cxxviii., p. 183. 

•^Bull. d. Soc. Roy. d. Sciences Med., etc., Bruxelles, 1897, No. 7. 



LEUKEMIA. 



457 



eight with 880,000 red cells, 305,000 white cells, and 39 per cent 
of haemoglobin. It was apparently of the myelocyte type. E. 
Mliller thinks that there are about five other ( German) cases on 
record, all of acute leukaemia and all with a similar blood count, 
though in some the large lymphocytes (without neutrophilic gran- 
ules) have been described as "myelocytes." 

Mliller' has lately reported with great care three cases of leukae- 
mia, all of them in boys four years old — all apparently acute, all 
of the gastro-intestinal type— /.e., the glands and follicles through- 
out the whole length of the alimentary tract being the chief seats of 
infiltration, though the liver and spleen were also enlarged. The 
counts were as follows : 





Case I. 


Case II. 


Case III. 


April 
30th. 


May 1st. 


May 2d. 


May 3d. 


White cells 


1,508,000 
109.500 
40% 


1,684,000 
93,800 


1,362,000 
46,000 


1,232,000 
6,800 
Death. 


2,290,000 
206,000 
25^ 


1,308,000 
420,000 


Polymorphonuc 1 e a r 

Small lymphocytes^. . 
Large lymphocytes . . 


2% 

85% (8-10 (u, diameter). 
13^ 


Many. 
Few. 
Few. 
Many. 


1% 

\h% 

84% 


.7 

2. 

97.3 
.01 




Few. 
Few. 


Two n o r m o - 
blasts seen in 
counting 
1,135 1 e u - 
oocytes. 


Seven seen in 
counting 1,118 
leucocytes. 



1 Jabrbuch flir Kinderbeilk., 1896, vol. xliii. 

2 All with large pale nuclei. 



PART VTI. 

EXAMINATION OF THE SERUM. 



CHAPTER XV. 

THE CLUMP REACTION. 

Gexeral Descriptiox. 

Although this plienomenon is to be obtained in various infec- 
tions, natural as well as experimental, and with various body fluids, 
I shall describe as a typical case of it the reaction which may take 
place when the serum of a patient ill with typhoid fever is added in 
certain proportions {^vide infra) to a young bouillon culture of well- 
certified and virulent typhoid bacilli. In a drop of such a mix- 
ture, examined between slide and cover-glass' with a magnification 
of 300 diameters or more, we notice, at once or within thirty min- 
utes, a marked slowing of the progressive movements of the bacilli 
or an unequal distribution of them in the different parts of the 
preparation. Whichever of these changes occurs first, the slowing 
of locomotion or the tendency to grouping, the other soon follows, 
and then both processes go on together, as admirably described by 
Biggs and Park r 

" Some of the bacilli soon cease all ^progressive movement, and 
it will be seen that they are gathering together in small groups of 
two or more, the individual bacilli being still somewhat separated 
from each other. Gradually they close up the spaces between 
them, and clumps are formed. According to the completeness of 
the reaction, either all the bacilli may finally become clumped and 
immobilized or only a small portion of them, the rest remaining 

' Hanging-drop preparations are often recommended, but a simple slide 
and cover-glass are as good for tlie purposes of this reaction. 
- American Journal of the Medical Sciences, March, 1897. 



THE CLUMP REACTION. 



459 



freely motile, and even those clumped may appear to be struggling 
for freedom. ^Yitll blood containing a large amount of the agglu- 
tinating substances all gradations in the intensity of the reaction 
may be observed, from those shown in a marked and immediate 
reaction to those appearing in a late and indefinite one, by simply 




Fig. 5U.— Partial Reaction. Fig. 51.— Typical Clumping. 



varying the proportion of blood added to the culture fluid " (see 
Figs. 49, 50, and 51). 

The process may go on gradually and be much more distinct at 
the end of half an hour. 

The groups or clumps above described constitute the important 
part of the reaction for diagnostic purposes. Of the loss of motil- 
ity more will be said later. 



460 



SPECIAL PATHOLOGY OF THE BLOOD. 



Technique of the Clump Eeaction in Typhoid Fever. 

Our account of the methods of obtaining the clump reaction may 
be divided into the following parts : 

1. The body fluids to be used and the methods of obtaining 
them. 

2. The cultures. 

3. Dilution and the time limit. 

1. The Body Fluids to be Used. 

Experiments have proved that the reaction can be obtained with 
the following fluids : 

(a) The whole blood, fluid or dried. 

(b) The plasma and serum, fluid or dried. 

(c) Also blister fluid, the fluid contents of normal serous cavi- 
ties, breast milk, pus, tears, and other body fluids. 

Of all these fluids, the blood, or the serum, fresh or dried blis- 
ters are the only ones used in clinical work. 

1. Use of the Whole Blood — Fluid. 

The advantages of this method are {a) its quickness, and (h) the 
small amount of blood [one droj)) sufficient for the test. 

I have used this method in most of my cases and always found 
it satisfactory and convenient. 

Procedure. — Suck up some water with a medicine-dropper and 
expel ten drops of it into a watch-glass. Then empty and dry the 
dropper, draw up from the watch-glass the ten drops just expelled, 
and mark with a file on the side of the dropper the point up to 
which the ten-drop column extends. Mark also the point to which 
one drop (expelled and then sucked up again as before) will rise. 

Ten drops of the bouillon culture of the bacilli to be used are 
then expelled into each of several small test-tubes, and one of these 
tubes is carried to the bedside. After pricking the ear as if for 
blood examination' (see page 7), put the end of the medicme-drop- 
per into the blood drop, and carefully draw back the rubber bulb 
(which has been previously pushed down over the glass part of the 
dropper) until the blood rises to the mark for one drop. Wipe 
from the outside of the dropper any blood that may adhere there 

^ Squeezing and milking the ear are of no harm in this procedure and en- 
able us to get on with a trifling and painless puncture. 



THE CLUMP REACTION. 



461 



and then expel the drop into one of the little test-tubes containing 
the ten drops of bouillon culture. In this way blood can be taken 
for examination from a dozen patients in as many minutes. 

2. Whole Blood— Dried. 

The advantages of the method are (a) the ease and quickness 
with which the blood can be obtained, {h) the convenience for trans- 
portation by mail, and (c) that it does not deteriorate or become 
contaminated by bacterial growth, as specimens of fluid blood or 
serum are so apt to do. Its clumping power is fully equal to that 
of the serum in most cases.' 

Frocedure. — The blood should be dried either upon a glass slide 
or on a piece of glazed paper or card. Any absorbent substance is 
less available. Glass is easier to sterilize than paper. Several 
large drops should be placed in different parts of the glass or paper 
and thorouglily dried. 

If paper has been used, we cut out the dried blood drop with a 
pair of scissors, keeping close to the blood all round, and drop it 
into a test-tube containing one or two drops of water, m which with 
some sharp-pointed instrument we mix the dried blood, freeing it 
as well as possible from the paper. 

To the liquid so obtained add eight or nine drops of the bouillon 
culture of bacilli and proceed in the ordmary way. Or we may 
drop the fragment of paper holding the blood directly into ten 
drops of bouillon culture— using the bouillon itself to soak off the 
hlood from the paper. 

The Fluid Serum. ~ 

The ear is pricked in the ordinary way and about twenty drops 
are forced out by strong squeezing. The blood is received in a 
small (preferably two-inch) test-tube. 

The blood when collected may be at once centrifugalized, and 
the plasma used for the test, or we may wait till clotting occurs 

^ ATidal and Delepine think the fluid serum is slightly more powerful than 
the dried blood. Johnson admits that in one-tenth of the cases the serum is 
the more poAverful. I have obtained reactions with the dried blood in only 
seven-eighths of the cases in which I got them with the fluid serum. 

- Some observers gather the blood on a bit of tinfoil and later crack it off, 
and after weighing it can make exact dilutions. Or we may soak blood into 
bits of filter paper of standard size and porosity and thus acquire a known 
amount as a basis for exact dilutions. 



462 



SPECIAL PATHOLOGY OF THE BLOOD. 



and use the sernni. ^Ylien blood is collected in test-tubes, it is 
convenient to free the edges of the clot from the tube all round 
with some sharp instrument, so that the serum may not be pinned 
down underneath the clot, as it often is. If this is done, a drop of 
serum can be had within two or three minutes, and is then mixed 
with ten drops of bonillon culture, as above described, and examined 
at once between slide and cover-glass. 

(Dried serum can be used in the same way as dried blood, but 
has no special advantages and has not been frequently employed by 
any observer.) 

2. The Cultures of Typhoid Bacilli to be Used. 

1. The stock cultures grow best on agar at room temperature. 

2. Ordinar}' peptone bouillon, free from sediment, is the best 
medium for the test culture. It should be just on the verge of lit- 
mus acidit}^, giving no blue to the red paper and requiring 3. 5 per 
cent of normal alkali to render it neutral to plienolphthalein. 

3. The cultures should be young — that is, the transplantation 
to bouillon should have taken place not more than from twelve to 
twenty-four hours before the culture is used. 

4. The virulence and motility of the culture are very important. 
Most observers agree that the more virulent the culture the more 
readily and characteristically it is clumped by typhoid serum. 
Biggs and Park noticed that one culture of peculiarly great viru- 
lence recently received from Pfeiffer of Berlin worked much better 
in their cases than any other of the cultures used. 

Cultures fresh from an autopsy usuall}' show motility, 
the bacilli darting about lilve a swarm of insects, but after repeated 
transplantations and long sojourn in the thermostat a good deal of 
this motility is gradually lost. Cultures J^ejd at room temperature 
preserve their niotil it>/ for much lonyer 2)eriods. 

For those who have no opportunity to test the virulence of or- 
ganisms on animals, the motility is the best guide to virulence, and 
the rule should be : Among the availahle cultures select tli at having 
the most rapid motllitij. 

4. Certain cultures contain small clumps of bacilli before any 
serum has been added to them. This is a very important point and 
has doubtless misled many. In consequence of this possibility 
every culture must be examined each time that a test is made. 

5. It is hardly necessary to say that the cultures used must have 



THE CLUMP REACTION. 



463 



been submitted to all the regular tests for the recognition of the 
typhoid bacillus, and that the greatest care must be used to avoid 
their contamination. 

The Use of Susjjensions or Ernuhions of the Bacilli instead of 

Cultures. 

A few observers — particularly Durham and Grliber — have pre- 
ferred to use a mixture of small bits of solid agar culture and bouil- 
lon instead of bouillon cultures. The majority of writers prefer 
cultures. 

The Use. of Attenuated Cultures. 

Johnson finds that with his methods of technique (dried blood 
and no definite dilution) pseudo-reactions were not uncommon with 
the blood of healthy people. 

He avoids this by using attenuated cultures — i.e., old stock agar 
cultures kept at room temperature and not transplanted more than 
once a month, from which he planted his bouillon cultures. This 
gives a bacillus of reduced virulence and slow, gliding motion, 
which is clumped far less readily than the virulent varieties. 
Bouillon cultures of this kind from twelve to twenty-four hours old 
he found to react in fifteen minutes with all typhoid sera and not 
with other sera even after forty-eight hours' waiting. 

3. Dilution axd the Time Limit. 
/. Dilution. 

I have mentioned without explanation in various parts of this 
chapter that the blood serum or other fluids used must be diluted 
with at least ten times their volume of bouillon culture before any 
observation is made as to their action on the bacilli of typhoid fever. 

The reasons for this dilution and for the proportions 1 : 10 are 
the following : 

It has been found, as mentioned above, that the mere formation 
of clumps in bouillon cultures of Eberth's bacilli is not a power ex- 
clusively possessed by typhoid serum. The serum of j^ersons suffer- 
ing from other diseases and even of healthy persons will form 
clumps exactly like those formed by typhoid bacilli, provided it is 
not diluted. The only known peculiarity of the typhoid ■ serum is 
that its clumping power is greater than that of other diseases, and 



464 



SPECIAL PATHOLOGY OF THE BLOOD. 



persists in spite of dilution, while the sera of diseases other than 
typhoid lose their power to clump typhoid bacilli when diluted ten 
times or more. 

//= Time Limit. 

But even this statement must be further limited. The sera of 
various other diseases, and of healthy persons, will sometimes 
clum]o typhoid bacilli even in a 1:10 dilution, provided ive givetJiem 
time enoiKjli. We must therefore limit the period within which a 
serum must " come up to the scratch " and do its work, if it is to be 
considered a typhoid serum. 

Following Griiber and Durham, a time limit of one-hcdf hour 
has been adopted by G-rlinbaum, Block, Haedke, Park, and others. 

All that these more or less arbitrary figures stand for is this : 
that hitherto no one has rejjorted any considerahle number of eases in 
which the serum of any disease or of healthy 'persons has clumpjed 
typjhoid bacilli udtltin one-half hour, when diluted 1:10 and vsed 
with unimpeachable technique. 

Tlie MicroscopAccd Examination. 

An artificial light is preferable. The u.se of hanging-drop prep- 
arations is unnecessary, as a simple slide with cover-glass is satisfac- 
tory. A hanging-drop cell may be extemporized by cementing with 
marine glue a small brass curtain ring to a slide, and inverting the 
cover-glass within it, as ad^dsed by Stokes. 

I have collected over 3,000 cases of supposed typhoid fever in 
which the clump reaction was tested as above described either with 
the fluid or dried blood. Of these, 95 per cent showed a serum 
reaction at some time in their course ; 2, 500 odd controls showed 
about 2 per cent of positive results in cases other than typhoid. 
Altogether then about 5,500 cases have been tested. If we leave 
out the reports of those whose experience covers less than 100 
cases, we have left 4,339 cases observed by 18 i^hysicians in which 
the percentage of error is 2 per cent only. 

Hvii' >'<irly does the reaction apjpjear? 

Few of the many observers who have written on this point have 
discussed how the beginning of the disease is settled and what they 
mean, e.rj., by the "fifth day of the disease." It might be dated 
from the first day of malaise and indisposition, from the nose-bleed 
or the beginning of headache, or from the time of going to bed. 



THE CLUMP REACTION. 



465 



Allowing for such serious uncertainties as this, we find that 
while the majority of observers record the sixth to eighth day as the 
earliest on which the reaction appears, there are quite a number of 
cases mentioned in which it was seen on the fourth or fifth day ; a 
few record reactions present on the third day, and two or three on 
the second day. • 

Hoiv late in the disease does the reaction last ? The majority of 
observations agree that in mild cases the reaction may die out even 
before the end of the fever. On the other hand, the reaction usually 
lasts several months, and Widal found it still present after one year 
in 3 out of 22 cases in which he tried it. These 3 subjects had had 
very severe cases of typhoid three, seven, and nine years previously. 
It has been reported present twenty and even thirty years after the 
fever. 

The reaction almost always persists in relapses, even to a second 
or third relapse, and occasionally it is present only in relapse and 
not in the original attack at all. Biggs and Park record a case in 
which the diagnosis was proved during the original attack by punc- 
ture of the spleen, which showed a pure culture of Eberth's bacilli, 
yet no serum reaction was present until the second day of the re- 
lapse. I have observed several similar cases, and quite frequently 
not found the reaction until convalescence. The failure to follow 
up such cases as these accounts for many negative reports. 

The Intensitij of the Reaction. 

Widal and Sicard record clumping with a dilution of 1 : 12,000 
and 1 : 1,800 and consider that in the active stages of the disease a 
dilution of 1 : 60 or 1 : 80 does not usually present the reaction, 
while in convalescence the power of the serum falls off gradually 
and is not always present even at 1 : 10. 

Biggs and Park find one-half their typhoid cases furnish serum 
with the power to clump in 1 : 40 dilution by the end of the first- 
week, and have occasionally noted the reaction even with a dilution 
of 1 : 200. 

Control Cases. 

Out of over three thousand cases of various diseases not typhoid, 
not over a dozen have been proved to clump typhoid bacilli with 
proper technique. It is quite possible that further improvements 
in technique may enable us to prevent even this very small error. 
30 



466 



SPECIAL PATHOLOGY OF THE BLOOD. 



Summary of Clinical Evidence on the Sero-Diagnosis of 
Tyj^hoid Fever. 

The blood of over ninety-live per cent of all cases of typhoid 
shows a clumping power in some part of their course, but in at 
least half the cases this does not appear until the second week of 
the disease, while in a small number of cases it first appears in 
relapse or convalescence. The clumping power may disappear 
before the defervescence and may be present only eight days in all ; 
as a rule it persists from the sixth or eighth day until convalescence 
is established. 

In diseases other than typhoid a clump reaction is very rarely to 
be obtained, provided a dilution of at least 1 : 10 is used with a time 
limit of one-half hour. There is no one disease in which clumping 
is especially apt to occur. 

Clinically the reaction is of considerable value, especially when 
the diagnosis is in doubt after the first week of the disease. 

Sero-Diagnosis of Diseases Other than Typhoid. 
1. Cholera. 

Grliber and Durham first showed that human cholera serum 
would clump cholera vibrios, following the researches of Pfeiffer m 
vivo by demonstrating a similar reaction in vitro. 

Achard and Bensaude have applied this to the actual diagnosis 
of cholera in man with considerable success. In fourteen cases, 
thirteen clumped readily ; two of these were on the first day of the 
disease. Thirty control cases were negative. The presence of the 
pellicle renders it unsafe to use bouillon cultures except such as 
have no pellicle, for bits of it are much like true clumps. Suspen- 
sions of twenty-hour gelatin cultures are more convenient. The 
dilution and time limit are the same as in typhoid. Some cases will 
react even in 1 : 120 dilution. The reaction can be performed with 
dried blood and persists into convalescence (seven months or more). 

2. Malta Fever. 

Wright and Smith tested the serum of 15 cases of Malta fever 
with the micrococcus melitensis of Bruce, and found a strong clump 
reaction to occur (1:50 in most cases). On the typhoid bacillus 
the serum of these cases had no action. Sixteen cases of typhoid 



THE CLUMP REACTION. 



467 



showed no reaction with Bruce' s organism. The evidence in favor 
of this organism as the cause of Malta fever is strengthened by 
these facts. Wright's observations have been confirmed by Xeus- 
ser and others in this country. 

Curry in a very recent number of the Boston Medical and Sur- 
gical Journal reports eighteen cases with clumping. 

3. The Bubonic Plague. 

Zabolotny' studied forty cases at Bombay in April, 1897, and 
found the reaction absent in the first week, present in 1 : 10 dilution 
in the second week, and in 1 : 50 dilution in the third or fourth 
week. He noted that the action of the infected serum seemed to 
deprive the bacilli of their capsules. In an editorial in the Arch. 
Busses de Pathologic, May 31st, 1897, it is stated that the reaction 
increases in intensity until the fourth week of the disease and then 
declines ; also that it is most marked in the severest cases. Fein- 
del {loc. cit.) states that in the acute pneumonic cases the reaction 
is absent. 

^Deut. med. Woch., 1897, p. 393. 



APPENDIX A. 



Neusser's Perinuclear Basophilic Granules. 

Using the following modification of Ehrlich's tricolor mixture, 
Neusser* believes that he can bring out certain characteristics in the 
leucocytes of value in diagnosis and prognosis. 



Cover slips stained with this mixture show in certain diseases 
{e.g., gout, leukaemia) a grouping of dark blue-stained granules 
around the nuclei of the mononuclear leucocytes and over and around 
the nuclei of polymorphonuclear leucocjrtes. These granules ap- 
pear to take up only the basic part of the tricolor mixture. 

For Neusser's conclusions regarding the meaning of these gran- 
ules, the reader is referred to pages 274 and 351. The researches 
of Futcher have in my opinion utterly disproved Neusser's claims. 
The granules are of no known clinical significance and certainly 
have no direct relation to gout or any other alloxuric diathesis. I 
have a triple stain {not made up for the purpose) which brings out 
Neusser's granules in every blood, normal or abnormal. 



i Acid fuchsin. 

Saturated aqueous solution of •] Orange G 

( Methyl green 



50 CO. 
70 " 
80 " 
150 " 



Distilled water . . 
Absolute alcohol 
Glycerin , 



80 " 
20 " 



Wien. kiln. Woch., 1894, No. 39. 



470 



SPECIAL PATHOLOGY OF THE BLOOD. 



Remarks. 




De- 
formi- 
ties. 


+ ++ 


Diameter. 


-H : 1 


ll 
1- 


; ; ; 


Normo- 
blasts. 


g : : 


•sajijoiaini 




•saiiqdouisoa 




■s8j.^ooqduiA[ 




•sjBapnuiiod 




•pajnnoo 
sajAOOonai 
JO aaqran>j: 




•uiqoiSomaBq 


"85' 

30 

37 
35-40 
85-40 


White 
cells. 


2,000 
4,000 
Normal . 
1,700 

Normal . 
Normal . 

Dimin, 

6,000 
19,000 
10,000 
10,000 


Red cells. 


2,211,150 
2,755,000 
1,220,000 
1,240,000 
2,211,750 
2,262,000 
680,000 
564,000 
564,000 
582,000 

1,288,000 
1,910,000 

1.768,000 
1,980,000 
2,220,000 
2,884,000 
2,458,000 
842,000 
1,500,000 
1.460,000 
1,680,000 

1,850,000 


Pate. 


CC ?0 L-? O 00 Oi 
00 00 00 00 00 00 00 
00 00 00 00 00 00 x> 

1—1 tH t-H t-H t-I ! 

^x C >^<zf2 C ^C^ 


d 


-rH 05 CO ic :o 



APPENDIX. 



471 



+ , it , I ++++ ,^^+ 4- 

++++ + + ++++ +^-+ + 




CO 



y—t CO 



1 ;i 



§ ^liiiiiiiVg+iiiiiii 

s il-SSSSJ'-'^ll -S3- 



IliiiiEiiiiiiiisiiiii 
i ii ii liiil ii i 11 ii ill PJ'ii^ 



ill 



1 I 1 11 iail 



I 
I 



1 



472 



SPECIAL PATHOLOGY OF THE BLOOD. 



Remarks. 






_L_ 

+ + T , I + + 
+ ^ + ++ + 






ii 


r-' CO CO • • OO 00 CO a 


Normo- 
blasts. 


L-r lo • • • CO CO a 

: ^ : : : 1 : 


•sajiDoiaXui 


. . - • 

Cvj LO -rH • • CO tH Cvj 


•sanildonfsoa 


00 ^ lO 


•s9aioot{duiAl 


L-O CO 00* • 1-C iC i-'T O 
CQ CO T-i CQ C<J CO CO 


•saBaionuiiod 


Lo 00 i> • • 00 00 o" :o 
i> :£5 :o i-t 


•pa^nnoo 

saiXooonai 
JO jaqran^^ 


o o o • • o o o 

O O O • • O O O c;^. 
LO 1— 1 • • IC IJt 


;uiqoiSoma6q 


L~ o 00 i-^r X o • o o X • • • • i-t X CI o o CI o o io 

tH Gv? CI i> ■-— C I CO • C? th . . . • CI CO '^t X l-O T-i tH 


White 
cells. 


; o 


4,000 
8,000 

1,000 
2,000 
4,000 
9,000 

7,500 

7,000 

4,720 
13,000 

4,000 
52,000 
700 
12,000 
16,000 
11,800 
10,000 

5,200 
800 

8,000 


Red cells. 


o o 
o o 


550,000 
784,000 
1,500,000 
1,500,000 
785,520 
1,500,000 
1,768,000 
1,088,000 
1,868,888 
2,820,000 
2,780,000 
2,200,000 
1,880,000 
1,890,814 
1,600,000 
1,288,000 
2.568,000 
2,256,000 
4,032,000 
8,464,000 
2,888,000 
3,080,000 
2,728,000 
806,000 
608,000 


Date. 


Oct. 2d 
2d 

l()th 
Nov. 27tli 
Jan. lOth, 1801 
Feb. 17tli 
Jiiiu! lOth 
Muy lOth 

81st 

24tli 

JUIK! 8tll 

July 8()tli 
Aug. inth 
Sept. 1st 
June nth 

July 27th 
Aug. 2d 

14th 

28d 

Sept. 12th 

27th 
Nov. 10th 

80th 
Dec. 8(1 
Aug. 22(1 

24tli 




X Ci O ^ CO LO 
tH T-l Ci CJ C^ C? CI CI 



APPENDIX. 



473 



++ 



+ 
+ 





o o 




C3 C C3 i> ^ 


C3 lO 








CO ^ O Oi C3 to 
iC O T-H (?3 


CO 0? 








C3 iO 










oi 00 ^ oioo CO 


C3 oi 








a a CO 


iO 00 








1-1 lo a CO 


T-i CO 






lO 


00 l> 


iO 






iO 


CS !0 Oi 05 "rfi 
i-H CQ 03 03 03 CO 


CO C5 

^ (>3 








00 OS 


IC 






oi 


CS ^ O O tH 00 

o i;o CD CD lo »o 


a ci 






o 
o 


o o o 2' o 
o o o S o ^ 

IC JO IC tH CO 


1,000 
400 


lCCQCOiOOOJOiO?>OOQOa0005QOOOiO}>OaOOOlO-<*iiOiCCOOC^--ilOT--iiOO 


o o • • • o o • 
o o • • • o o • 


o o o o o o • 
o o o o o o ■ 
o ^ C30 o i> o ; 


• • o o o o o 

• -000300 

; ; ?o C30 io ^ o 


•ooooooooooooo 
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■O^OTHCO■r^^OOOCQ^OOOO 








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o o o o o o^o ooooooooo o^o o o o^o o o o 

'rj^ C3 C3 CO" OO" O' O"" O' OD" of OO" OO" CO" lO of of O' of of iO CtT CO o' 
CDOOt--'HCO^rlHOO-*)OOOIOCOCC'OS0500 0iCOl005iOOOO 
OJOOOCOiOCOODOOOJCQlOO-rH-r-lOOOOSOOOCOt-^lOOOCD 

T-T -r-T of of T-T co" of co' co' th -th" th th t-T t-T of t-I" t-T th of co' of 



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00000000 03 0 

oo-^oooooioo 

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a 

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CO ^ -rH tH Oi 03 th 03 03 03 CO tH -tH -r-t 03 tH 



+3 ^ 'tJ +3 

O CO .00 03 03 

CO bc<^ 



■5^ 00 
03 03 



474 



SPECIAL PATHOLOGY OF THE BLOOD. 



I 



•saiAooiaAui 



+ ±+ 



+ 



•saiiqdouisoe 



C3 OO 

CO O CO ' tH 



•saiiooqdmAi 



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cs 00 


CO 




auao aaj 


00 T-( CO i> 




l> 00 


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O iO 


•pajunoD 


o o g o o 


o 


o o 


sajAooonai 


o o g o o 


o 
o 


o o 

C4 00 


JO jaqranM 







•uiqoigouiasq 
5uao jaj 


O X) O CQ J> GQ 0-"? lit 
CO C9 CO iC CO ^ 


07 
CO 




• O T-^ O O X O i> • lirr i> o o? 
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• CO Tj4 

• 1—1 1— 1 


hite 
(lis. 


• o o o o o o o 
; i> ic ic c3 ^ o JO 


o 
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• o o 

• o o 

; o o 




• T-T oo" co' o~ of of 


£> 


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• of co' 


ells. 


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o_ o — o o o o o 


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• o o 


ledc 


:c o' x' x' x' 
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CO O? Ol O CO 01 i-C 


co' 

CI 


07(1 


o' -f of o' co' o' '^'^ o' o" of o' M^" co" 

OXC:C0C0i-0OO-^i>05^Ci 
'^COCCOOlCO^lClOOOCO-r-'O 


624, 
896, 




T—T co" co" co" co' co" cc' 




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T-T -r--' T^' of of of CO" T-T tH tH -r-T 









■^ot^-^OTor^T2-^^>oioiHxx?--5oiH'SSco 

T-H T-i Oi 1—1 T-H OJ O"? 0^07 0^ 03 CO 1-t 03 0> O? O? i-i 



03 0> O? O? 



6 



CD 
CO CO 



CO 



APPENDIX. 



475 



++ ++++++++ 



+ 



+ 



+++ + 



+ 



+++ 
+++ 



O O O O i-i 05 CO O O • T-i 



GO 30 <a5 


. . . CD . .to 


. to C3 00 




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■ • (M i-H CO T-l • 


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C5 


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CO CO -rH -r-i tH 


• • • 00 00 CO CO T-4 o o 

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C5 O i> Oi CO 05 
lO ^ »0 lO 03 


lO 

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00 00 05 




C<> OS O Ol ID T-H 
X> iO i> CO ID 00 00 


• • • 00 O CO CO J> Oi CO 
CO i:- 00 i> CO 


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^ 


o o o o o o o 
o o o o o o o 

00 iC O iC o ?0 iC 


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. o o o o o o 
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C3 CO 'rfi • -rH th T-i 1-H T-i CO 03 1-1 CQ CO (?5 03 • • 


COlOi> • • •CQ^'^O'^'* 
<M 03 T-l • • -co • CO CO CO Thi iO ^ 



o • o o o o o o o o o o o o o 

O •000 10 10 000000050 

O lOCDCOt-t-iOiOOit-COOOOO 

co" • lo' J> io' oo' co" oo'' co" -Tt^' co" co' co' TtT 



OOOOOOOO'^OOOOOOOtHCO'* 
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lOOOOOOOOJCO SooO-rHOO'iTHTtHCO^-* 



f> i> lO ^ 



05 OJ T-l o ^ 



O -OOOOOOOOOOOOOOOOOOOOOO OOOOOOOOOO 

O -OOOOOOOOOOOOOOOOOOOOOO -OOOOOOOOOO 

O -OOOOOOOOOOOOOOOOOCOOOOOr^^OOOOOOOOOO 

of ; oo' o' co' o" o' co' 'Oo' co' co' o" oo' co' o' o' co' oo' ^ co' ?>' oi' o' oo' 05 -rh oo' otT -*' 

iO .0500 0'?C000000101C0Q0C005C0l0OCC01i>0i^«>lOLi:05 01i--^O00-rHC0 0'JlO00 

i> .O5OSiO-rHO5'r-l00tO^O5O5'OC0OiQ0C--O5CO-^C0O5t--^T— lCOQO*OCQO?'^COaOOi 



05 T-l -rH 



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>0i-^C0OC0C0O»0C0C0C000«0T-'0iiOt-CQ£-T-H 
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^ ^ ^ J3 ^ 

Tj -U +J -t^ ~ +^ -M 

CO 05 00 03 CO O 
— ' T-i Ol CO 



476 



SPECIAL PATHOLOGY OF THE BLOOD. 



+++++ + 
+++++ + 



m + 



++ 



+ 



IC T-l 05 CO O 



00 «D -rjl 



T-l lO -r-l • 



•saiiqdouTSoa 



CO CO 
^ C5 lO ■ tH 



•sa^AooqduiA'i 



•saBaionuXiod 
■juao aad 



•pajunoD 
JO jaqrariN 



o o o o o 
o o o o o 

LO C 00 lO CO 



lO o 
Ol o 
r-l i;- 



O ^ J> 
»0 CO C5 
CO <M 



•inqoi Somas q 



+ 



11 



O O O O '3 o 
O O O O § JO 
O ^ O p ^ 

co^c^fco" o' o <^ 



ooooooooo -o 

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o o 
o o 
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o o 
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CO CO 



o o o o 
o o o o 
o_o o o 

iO 00 00 ^ 
tH CO CO 



ooooooooooooo 
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o o o o o o^o^o^o^o o^o^o^ 

O' O' OO" 'OO" o' o" o" co' 

00THcXit-OC1O'*-^C0C9t-O 

CQCOOT-iOOCO-rHOOCQCOi>i>t- 



o 


o o o o 


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(M CO C3 T-^ CO th t-( O"? CO t-h -~ 



■I O^ 



CO CO 
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lO 05 CO 



APPENDIX. 477 



-1- 

1 




+4-4-+++ 


4-i~F?i 7; 
1 (JJ JJ. 


+ 
+ 






+ 


++ 
++ 


: + 




+++ : ; ; 


++ i i 


+ 






+ 


























CO o - • • • 


T-' 1-H CO GO 






Oi 










^ CO 


CO . . 
CQ^O • • 








^• 


CO . 

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COCOrH- • 










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ate CO 

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i 


















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^§ 










£ 


CO 

o 






11 


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i-iiii 


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i 


1 


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05 Oi O-f C3 c ^ 







• 00 • o' g^' • 





^'co 



mmmm 



1 



mtimm 



i ii 

II .iii||i||ii||||pp3iiiiii|l|i|i 



II f 



I I ^ 



i 



II I 



478 



SPECIAL PATHOLOGY OF THE BLOOD. 



t4 



+ 



+ 




Oi a CO a ^ o'i 



•seiAooieAra 



X' 

^' JO i> C3 



O X ^ O t-i C3 l-C 
(73 CO T-' 'g^' oi ' ' ' 



•saitqdouisoa o 
juao ja j CO 



X tH ^ 

T—t T-i T-H 



T-! ■ i-^ ' T-^ CO i-- 



•seu'-ioqdinAi 



siBapnuAlod 



X X CO 



•paiunoo 
sea.^ooonai 
JO aaquinM 



o 
o 



i> O 03 O O 
C3 O O 05 
CO iC O X CO 



OOOOOOC O OC: 
c^. OOOOOOO O OX 

ir^ ic ic CO Lf i-T T— c-i 



•uiqoiSoniseq 
iuao J8d: 



o o o • • - o • • o 
o o o ■ • • o • • o 
CO o ; ; ; X ; ; th 


o o o o 

i> O ^ CO 


o 

X 


; * ^ S 


o 


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o 
25 


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... . . C5 


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co' 






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o o o o 
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o o o o 


o 


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o o 


:o ^"o'c^f x'o' o" ! ; 
X ci o L-:^' . . o 

COC5^«5^XM^ . .X 


o'io -^"o" 

O -rH CD O 

CO J> o i.-- 


o' 

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CO 


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T-H -Tti CO C^O i>- X (75 Jl' 
T-i-r-l-r-lC^ 



i;.- S X C5 O O — , 
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CI X 
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Ct X CO X 

5^ 



APPENDIX. 



479 



-1- 

1 








+ 4- 


1 +4- 1 1 ++ + 


+ 


+ 


+ 




+ + 


++I M 1 1 1 ::|: + 










lO 05 ^ 
«0 


CO • CO ^ i-H CO CO CO CO iO 
1-1 iO 


CO 




CO 




T-H OS CO 
tH 






















CO C3 C3 


O CO . C3 ... TH GO 










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• • CO T-l Ttl -rH 


C5 








CO 


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CO 


CO 




tH T-l CO 


• T-5 • C3 T-l tH C^' CO ' T-H ' 1-H 


00 








lO O? 00 


CQ C3 00 GO 00 C3 Oi lO 


«D 
CO 


<?3 


CO 


CO 


CO T-l T-H O 

CO CO ^ ^ 


OOlOOlO^xhlCOCOt-COO-rHGQ 
CO C3 C3 CO CO T- CO CO »0 CQ CO 


to 








''^liOiOO^C^CD'* ^co 


o 


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f> 


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?0 CO CO LO »0 O t~ i> CO CO 00 iO 'rt^ 00 o 


o 
o 


o 
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oooooooooooooooooo 
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OlOl010-r-IO?iCiOiOiO»OiOOi>^C<?COTtl 










1—1 





US 

CQ 
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a; 



o o o o o o 
o o o o o o 

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co'co'oi oo'c^ 



o o o o o o 
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CO O Oi CO CCf 

co" co' co' co' CO 



o o o o 

O O O CO 
03 0^05 



o o o 
o o o 

O O CO 



o o 
o o 
o o 

CvT-rH 

00 
CO iC 



oooo oo o o o o o o o o o o o o o 
oooo .oo . o o o o o o o o o o o o o 

O O O O^^r^ OO-T^OOOOOOOOOOO o_^o 

■ oo" Oi" co" O" . 2i co" co" O" O" O" O' CO* o" o" ^" oi 
^>CO''^^CO,-^^:-Oo<='^'^C'T^O■rHCOCOf^O■^OCOT^ 
Olt-COOD — cool— loC000Oi>^C3i>M^^(?-"> C0__05 

- ^ ^ r (^f t-h" T-T -ph" cq" T-T 



O O O o o 
o o o o o 
o o o o o 

co'^'o"*?^ co" 

00 CO T-H C9 o 
CO CQ CO »0 CO 



' o o o 
■ o o o 
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03 tH 






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1—1 





THCOOOSOSOOTHCOT-HlOOOST-iOS10COCOC0 03 00 03T-ii:OT-liOO?OOiOi>i>00300030S 
tH y-i^T-t ,O3 03 03 -tHt-^ 0J03 TH-rHO? i-tCO-r-lO^O^-r-l 



2 c3 O S 



00 



OS O tH 
00 OS OS 



^ IC CO l> 
O OS OS OS 



480 



SPECIAL PATHOLOGY OF THE BLOOD. 



^ a a 2 
§ ^ ^ I 

P (D «2 O 

^ S gj 
« O bD 

'^^^ 2 



+ + 



I :+! + 



+ +++ 



+ + 



+ :+++ 



+ +++ 



Megalo- 
blasts. 


tH T-H CD i> th O T-^ 




CO • -rH 


Normo- 
blasts. 


tH S<J • O i-H 05 CO 03 CJ CO • 

• CO 00 T-H tH -r-l 






•sajAooiaicu 


CO 00 . . CO 00 . 
CO T-H CO 1-1 • • CO (N • 1-1 


CO* tH CD* T-I 




•seiiqdonisoa 


^ 00 O-i 00 

T-i' c^' th t-I id ' T-I CO N 


.CD 

CD* iO* ^ ^ 


03 Tin 


•sejiooqdraAi 


C5 ^ 00 CD ^ 

-1— i-rfiiOCDt— 'iOCDiC}>0»OCD 
CO^CQCO^SQC-'J'^CQCOCQGQ 


c-? o c? ci 

CO C3 T-H T-H 


00 00 
tH O ^ CS 


•sjBapnnj^Iod 


^ 00 CD CO CD CD 00 

-<*GQT-i-rHCDCOi>00THOiT-i<?5 
CDiOi>CDiCi:~CD^CD10J>t>- 


59 
71 ■ 

71. 
75.2 


lO 00 00 

CD CD CO CD 
lO }>- o CD 


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JO aaquiriN 


OOOOOOOOOOOO 
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i010JlOOOiOOOi01010CiC5 

T-H tH 


o o . o 
o o . o 

-rH T-t , lO 


o o o o 
o o o o 

lO CD iO O 


•uiqoiSoraaeq 


OiClOOOOJCOiOiClOOlO 
CO-rH-,-HT-iC5CO-^T:JiC<JC^^10 




l> CD IC tH CI 
-rH CO CO T-H 


White 
cells. 


ooooooooooo • 
o o o o o o o oo o o • 

^GQCDt^COCDOOCDiCO ; 

(^frH oo'^cD'cico'c-i T-Too'co'o' • 

T-H T-H • 


13,000 
10,000 
11,500 

13,000 


o • • o o • 
o • • o o • 

05 ; ; CD T-H ; 

.' ^CD'^" • 


Red cells. 


OOOOOOOOOOOO 
OOOOOOOOOOOO 
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oo"" oo" c<f co" o" o" c-i io" ^f o" o"" 0*^ 

i>(MOO)OT-i05-rHCQ10000CO 
CQ00i>0ST-iQ0OTHlOC0O00__ 


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O^O^^O^O 0_^0_^0_^0__0_0 O' o__ • 

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<MCDOCDC0i0t-C^C<?C0i>O . 
CD -rtH i> iC rH CQ CD O . 


Date. 


^ ,a ^ j5^rP4^ 

T-lO5CD£-»O(^iiOlO00T-iC<i00 
T-l tH C3 C3 T-l 


'O-w-^.s-t^-M-l-i-l-i 0O-(-^-l-i-(-i-(-i+J 
COOiOilOlOOOCD-rHCDCDCSOOCO 

T-l C5 CO T-l T-H -rH 




May 

June 
July 
Aug. 
July 


Aug. 

Sept. 
Nov. 
Dec. 


July 
Aug. 


No. 


00 Ci o 
Gi O CI O 

T-H 




-rH 

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T-H T-H 



APPENDIX. 



481 



++ 
++ 



.+4- 
++ 



+ 



++ +1 + 



++ + ++++ 



■r-t T^l O -r-l C"? 



O • C5 iC • • CO • 03 C<J • Ot> C5 • • 

. C9 C^J 00 ^. ^. . 0^ . . . 

• c<i T-^ cqf t-h' • • ■ • ■ . - 

00 O «D O X) 00 ^ cTc^OO O iO ^ ^ O O C3 CD t^i -xt^ 

• ^ •^•■r^C<^iO^■r-IC0^10Tj^ .t-H-i-ItH THTt^ -tH-tHt-I^ -rH O5rHT-IC0C0 

CO 00 ^ ^ 00 O ^ 00 lO O 00 00 ^ 00 00 ^ ^ co" 

GOi>>'oCOCOOOCOO-rHOO"JOiJ>OOCO -OOCOOo'c-OO^' COOOOOt-hOI i>OOir-iqp 

CO O'? ^ CO p."? CO T-H ^ ;^t) CO CQ CO tH CO ^ C<? -rH Q-j GQ ^- C3 C<? CO Qj CO Oti C'^ GQ CO GQ 

O^CQC<>COQO GQ OOO^C-^ OiiO<:0 CO 01C<JG<JC0^^i:0 ^TfiOi 

■r-I O O CO 00 O CO CO CO CO ^ O O ^ - 00 O O-l C5 CO GQ G5 tH 00 CO O C5 iO o 

COi^-lOCOC^t-^COit^iOCOCOCOCOlCOO iOlCt^OOCOt- 07i>t^C0t-C0C0 f>t^OCOi>- 

o o o o o o o o o o o o o o o .oooooo ooooooo ooooo 

o o o o o o o o o o o o o o o .oooooo ooooooo ooooo 



o o o o o o o o o o o o o -ooo 

o o o o o o o o o o o o o -ooo 

i-H^iOC003^i>GQlOi>THTHO^ ;*OOG<i 

GQ o" Co" Oi CO' OO' iO IC i> CO' O" CO' JO • 05 o" J> 



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; of of co" o" o" oo" oo' oo" T-T go' co" of co' o" of 

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^^0iO-^■SS^^|^Ci00ioSclCi-^-5^O 

OJ 05 CO T-H O"? O"? T-H -rH OJ O"? T-H ■,-( -r-i O? t-i 03 03 Oi CO tH Oi O? O? CO rH OJ O"? 



CO |Zi 



31 



482 



SPECIAL PATHOLOGY OF THE BLOOD. 



4^ 



s 



-+++++ 



+++ 



++ +++++ 



i 



OCOt-h cOt-i t^ho COcr^L-TiSC?} CQ^OJiO 



•S8itqdouiso9 



15 i?r 

sg^o^ g^i ^^^^^ ;s^^^^g| 



•sjBaionaiiod 



•pa^unoo 
sajAooonai 
JO jaqmnNj 



1 11 i§ 11 iiili iiiiiii 



■uiqoiSomsq 



iiili Jliii :ii iiili M%%%m 



L-t a5~i--f i-'f J> i> CO 



iiiiiiiiiiiiii iiiii iiiii 
iiiiiiiilliigi iiiiH iii^iii 



iiiiiiiiiiiiii !-?■ • ■ • ■ i 



APPENDIX. 



483 



APPENDIX C. 



Table Showing Gradual Increase in Size of Red Cells during 
Convalescence of Chlorosis. 

Case I. 







Per 






Red Cells— Diametek. 








Color 
Index. 














Therapeu- 
tics. 


Date. 


Red cells. 


cent. 
Hgb. 


5.6 /X. 


7.0 IX. 


8.9 fi. 


9.8 ix. 


Aver- 
age. 












p. ct. 


p. ct. 


p. ct. 


p. ct. 


p. ct. 




May 16tli 
17th 


4,950,000 
5,247,000 


















Ovarian 
■ extract. 


41 


0.46 


5.0 


64.0 


31.0 


1.0 


7.46 




June Sth 


5,717,000 


44 


0.46 


1.5 


59.5 


37.0 


2.0 


5.55 




15th 


5,740,000 


57 


0.59 


1.0 


52.5 


41.5 


5.0 


7.71 






23d 


6,332,000 


61 


0.57 


4.0 


48.5 


42.5 


5.0 


7.68 






30th 


6,030,000 


61 


0.60 


2.5 


41.0 


49.0 


7.5 


7.85 




Blaud's 


July 7th 


6,375,000 


65 


0.60 


3.5 


38.5 


52.5 


5.5 


7.84 




- pill. 


17th 


5,730,000 


70 


0.72 


3.5 


41.0 


53.0 


2.5 


7.76 




26th 


5,687,000 


72 


0.75 


1.5 


44.0 


52.5 


2.0 


7.77 






Aug. 10th 


5,792,000 


72 


0.73 

















Case II. 



3,900,000 


30 


0.45 


0.5 


56.5 


43.0 




7.44 




4,398,000 


43 


0.56 


2.5 


51.5 


44.5 


1.5 


7.64 


1 


4,740,000 


49 


0.61 


1.0 


49.0 


47.5 


2.0 


7.67 


1 


4,730,000 


47 


0.59 


2.0 


48.5 


48.5 


1.0 


7.68 


J 


5,884,000 


57 


0.58 




38.0 


53.0 


9.0 


7.99 


5,667.000 


65 


0.67 


2.0 


38.5 


52.0 


7.0 


7.91 




6,437,000 


71 


0.65 


1.5 


39.0 


54.0 


10.5 


7.94 


i 


6,040,000 


71 


0.69 


1.5 


31.0 


59.0 


8.5 


8.04 





Ovarian 
extract. 



Blaud's 
pill. 



Case III. 



Oct. 


17th 


3,701,000 


27 


0.43 


2.0 


68.5 


29.5 




7.37 






24th 


4,855,000 


39 


0.47 


1.0 


61.5 


34,0 


3.5 


7.55 


] 




31st 


5,230,000 


53 


0.60 


2.0 


47.5 


45.5 


5.0 


7.74 




Nov. 


12th 


6,021,000 


72 


0.71 


1.0 


39.0 


59.5 


5.5 


7.97 


\ 




20th 


6,205,000 


80 


0.76 


1.0 


18.0 


72.0 


9.0 


8.24 


J 



Blaud's 
pill. 



Case IV. 



Dec. 


12th 


4,255,000 


40 


0.56 


1.5 


63.0 


35.5 




7.48 


( Blaud's 
j- pill. 




28th 


6,105,000 


65 


0.63 




52.0 


44.5 


'3.5 


7.72 


Jan. 


13th 


6,066,000 


71 


0.69 


2.0 


36.5 


60.0 


1.5 


7.80 



484 SPECIAL PATHOLOGY OF THE BLOOD. 

APPENDIX D. 



THOMAS R. BROWN'S FIRST CASE OF TRICHINOSIS. 

Showing Total Numbeti and Percentage of Various Kinds of Leu- 
cocytes. 



Date. 


Leuco- 
cytes. 


Percentage of Various Forms 
OF Leucocytes. 


Number of the 
per 


Various Forms 

C.MM. 


P. M. 

Neut. 


s. 

Monos. 


L. M. 

and f. 


Eos. 


P. M. 

Neut! 


s. 

Monos. 


L. M. 

and T. 


Eos. 


Mar. 5tli 


17,000 


55.0 


3.0 


5.0 


37.0 


9,350 


510 


850 




6.300 


6tli 


16,500 


50.0 


5.0 


7.0 


38.0 


8,250 


825 


1,120 


6,120 


7th 


17,500 


53.0 


3.0 


7.4 


36.4 


9,275 


525 


1,200 


6,300 


8th 


25,300 


60.9 


1.9 


5.9 


31.4 


15.000 


500 


1,500 


7,750 


9th 


22.300 


70.8 


2.0 


4.5 


22.7 


15,300 


440 


900 


5,060 


10th 


16,500 


74.7 


3.1 


8.0 


15.1 


12,000 


480 


1,280 


2,400 


11th 


21,167 


75.1 


2.8 


2.4 


18.6 


15,800 


630 


500 


3,700 


12th 


17,500 


77.8 


4.4 


3.0 


15.1 


13,600 


770 


510 


2,625 


13th 


18,833 


77.6 


2.1 


3.7 


16.6 


13,860 


380 


710 


3,000 


'14th 


13,800 


74.6 


4.3 


4.0 


14.9 


10,300 


580 


560 


2,100 


15th 


13,750 


74.0 


7.6 


3.2 


13.6 


10,300 


1,000 


420 


1,720 


16th 


13,250 


78.7 


5.3 


2.1 


13.8 


10,400 


680 


270 


1,700 


17th 


16,000 


73.2 


11.3 


1.9 


13.5 


11,700 


1,770 


310 


2,160 


18th 


17,750 


77.4 


10.9 


1.7 


10.0 


13,800 


1,970 


300 


1,775 


19th 


20,400 


71.1 


13.1 


2.3 


13.1 


14,200 


2,600 


460 


2,600 


20th 


15,700 


76.5 


10.1 


2.2 


11.2 


12,100 


1,570 


340 


1,760 


21st 


16,800 


72.9 


13.2 


1.8 


12.1 


12,400 


1,210 


320 


2,040 


22d 


14,000 


79.2 


10.8 


1.7 


8.3 


11,200 


1,540 


240 


1.130 


23d 


16,800 


73.6 


10.4 


1.6 


13.5 


12,400 


1,700 


270 


2,200 


24th 


19,600 


74.6 


11.2 


1.8 


11.2 


14,800 


2,200 


360 


2,200 


25th 


17,600 


80.4 


8.9 


1.6 


8.7 


14,400 


1,600 


290 


1,560 


26th 


24,000 


69.2 


12.7 


2.0 


15.4 


16,800 


3,120 


480 


3,700 


27th 


20,300 


69.9 


11.2 


2.2 


16.0 


14,000 


2,240 


440 


3,200 


28th 


24,100 


68.3 


10.1 


2.4 


18.9 


16,300 


2,400 


580 


4,560 


29th 


20,700 


69.4 


5.7 


1.4 


22.9 


14,000 


1,180 


300 


4,600 


30th 


22,300 


60.7 


9.6 


3.0 


26.0 


13,400 


2,200 


670 


5,720 


31st 


22,200 


57.4 


11 2 


3 2 


27.8 


12,600 


2,500 


680 


6,160 


Apr. 1st 


24,300 


60^7 


7.9 


3.4 


27.8 


14^400 


1^920 


840 


6,720 


2d 


23,800 


59.3 


11.6 


3.0 


25.0 


14,100 


2,760 


710 


5,950 


3d 


25,200 


53.3 


13.3 


2.8 


30.0 


13,300 


3,300 


700 


7,500 


4th 


23,400 


49.9 


13.3 


3.0 


32.8 


11,700 


3,200 


710 


7,590 


5th 


24,300 


48.8 


13.2 


4.0 


33.8 


10,100 


3,150 


960 


7,160 


6th 


24,700 


51.2 


14.0 


3.6 


31.6 


12,700 


3,500 


650 


7,900 


7th 


25,100 


48.4 


14.5 


2.5 


33.7 


12,100 


3.600 


625 


8,600 


8th 


29.600 


45.2 


11.6 


4.0 


38.8 


13,500 


3,450 


1,180 


11,600 


9th 


28,900 


45.0 


13.3 


3.2 


38.3 


13,000 


3,850 


930 


11,000 


10th 


24,500 


45.8 


12.2 


3.8 


38.0 


11,300 


3,100 


900 


9,300 


11th 


29,800 


42.2 


14.0 


4.0 


39.8 


12,600 


4,150 


1,180 


11,900 


12th 


28,000 


44.0 


14.8 


2.5 


38.7 


12,300 


4,150 


700 


10,800 


13th 


24,200 


42.0 


11.8 


1.4 


44.2 


10,000 


2,880 


340 


10,700 


14th 


33,300 


38.6 


13.2 


3.8 


44.0 


12,800 


4,400 


1,300 


14,700 


15th 


28,100 


34.8 


19.6 


1.6 


44.0 


8,600 


5,550 


450 


12,300 


' 16th 


25,400 


30.4 


16.8 


3.0 


49.6 


7,600 


4,200 


750 


12,400 


17th 


27,000 


31.8 


13.2 


3.4 


51.2 


8,600 


3,500 


920 


13.700 


18th 


35,700 


27.2 


14.4 


3.8 


54.6 


9,700 


5,140 


360 


19.500 



APPENDIX. 



485 



Date. 


Leuco- 
cytes. 


Percentage of Various Forms 
OF Leucocytes. 


Number of the various Forms 

PER C.MM. 


P. M. 

Neut. 


s. 

Monos. 


L. M. 

and T. 


Eos. 


P. M. 

Neut. 


s. 

Monos. 


L. M. 

and T. 


Eos. 




29 000 


9fi fi 

/CU. u 


19 0 

l/C. u 


o. u 


58.2 


7,700 


3 480 


1 040 
1 , u-±u 


1 ft QAA 


20tll 


19 200 


22.2 


12.4 


4.2 


61.0 


4' 200 


2' 350 


800 

ouu 


1 1 ftOA 


01 ct 


9q 000 

/CO, yjyju 


16.6 


16.0 


3.8 


63.6 


3^800 


3' 680 


870 


1 4 ROO 

14:, ouu 


90rl 


9R noo 


10.4 


18 8 

iO. o 


7.4 


63.4 


0 TOO 

/C, ( uu 


4 QOO 

'±, UUU 


1 Q^O 


1 ft ^AA 
ID, OUU 


/COU. 


17 700 


6.6 


19.6 


5.2 


68.2 


1 1 70 


3 400 


880 

oou 


1 1 A7A 
1 1 , U ( U 


94-th 


is' 800 


7.2 


23.4 


4.4 


64.8 


1 '^70 
1 , 0 < u 


4' 400 


840 

otu 


1 9 9An 
/CUU 


iCO 111 


l/S fiOO 

J, (J, UUU 


8.8 


19.2 


7.2 


64.8 


1 370 
1, 0 ( u 


2' 990 


1 020 


10 400 
1U,^UU 


/CO Hi 


17 000 


12.4 


14.2 


6.0 


67.4 


9 100 

/C, 1 uu 


2 410 


1 090 

1, U/CU 


1 1 4^0 


/O < 111 


12000 


2o!o 


8.6 


7.4 


64.0 


9 4.00 

/C, -lUU 


2' 030 


890 


7 700 
1 , < UU 




11100 


18.2 


17.6 


7.2 


57.0 


9 090 

/C, U/CU 


1 950 


800 


0, oou 


9Qth 


19 800 

1~/, ouu 


19.4 


19.4 


6.8 


54.4 


2 470 


2,' 480 


870 


fi QQO 

U, WKJ 


ROth 

OULIl 


13 200 


20.8 


17.2 


8.2 


53.8 


9' 700 
/C, 1 uu 


2' 270 


1.080 


7 090 
1 ,U/CU 


MaT 1 ct 


11 000 


21^8 


mo 


12.0 


50.2 


2,400 


1,760 


1,320 


5,520 




8900 


97 .4. 

/C ( 


17 8 


8 4- 


tu. ^ 


/0,4t4iU 


1 (^80 
X, oou 


74.0 


K 1 ftA 
0, iOU 




10700 


36.8 


15 0 


6.8 


41.4 


3,940 


1,600 


710 


4,430 


4tli 


10^700 


34.8 


20.8 


6.4 


38.0 


3,720 


2,120 


680 


4,070 


0111 


1 1 000 


45.6 


19.0 


6.6 


28.6 


5,020 


2,090 


710 


3,150 


6tli 


10,300 


41.0 


20.2 


4.8 


33.6 


4,220 


2,080 


490 


3,460 


7tli 


12,300 


50.8 


20.2 


6.0 


23.0 


6,250 


2,480 


740 


2,830 


8tli 


11,500 


54.0 


18.0 


4.0 


24.0 


6,210 


2,070 


460 


2,760 


9th 


11,500 


59.8 


17.6 


6.2 


16.4 


6,850 


2,020 


710 


1,890 


10th 


15,700 


51.0 


12.8 


5.6 


20.4 


7,100 


2,010 


880 


3,200 


11th 


13,500 


62.4 


14.2 


4.8 


18.8 


6,420 


1,920 


650 


3,540 


12th 


11,000 


64.0 


14.4 


4.8 


16.8 


7,040 


1,580 


530 


1,850 



BIBLIOGRAPHY. 



It has seemed to me best to give a list only of the books and 
articles which I have found most useful, since the general bibliog- 
raphy of the subject is now large enough to form a volume by it- 
self. Most of the larger works here described contain extensive 
bibliographies — especially that by Ewing. 

Text-Books. 

1. Ewing: "Clinical Pathology of the Blood," Philadelphia, 1901, 8vo, 
432 pages (Lea Bros.). This is the newest book on the blood and the fullest 
discussion of the theoretical points connected with diseases of the blood. The 
bibliography and resume of the work of other observers contained in each 
section are admirable. The original observations of the writer are contained 
chiefly in the chapters on malaria and diphtheria. The tone of the book is ad- 
mirably sane and judicial throughout. The illustrations are poor. 

2. Ehrlich, Lazarus, Pinkus, and v. Noorden in vol. viii. of Nothnagel's 
"Specielle Pathologic und Therapie," issued between 1898 and 1901 (Wien, 
Holder & Co.) have written a series of articles on ansemia, leukaemia, and 
chlorosis, which together amount to many pages 8vo. The clinical aspects 
and therapeutics of the diseases are included. The hgematology of the book is 
on the whole inferior to Ewing's, although parts of it, especially v. Noorden's 
study of chlorosis, are masterly. The articles on anaemia are interesting as 
they contain Ehrlich's latest utterances. The work is out of date in some re- 
spects owing to its characteristically Teutonic ignorance of important work 
done in England and America, but it is undoubtedly the standard German 
work on the subject. 

3. Hayem: "Du Sang," Paris, 1889, 8vo, 1035 pages (French). This val- 
uable book is the largest that I know of on the subject, and contains a mine of 
information on the morphology of the blood in health and disease, mostly 
from the author's own experience, literature being but little referred to. It 
contains a comparative anatomy of the blood and a long account of blood de- 
velopment. Unfortunately, it is dominated throughout by a theory of blood 
formation which has never gained acceptance by any other authority. It is 
very full on the subject of fibrin formation and of chlorosis. The illustrations 
are excellent. In a later work, "Lecons sur les Maladies du Sang," Paris, 
1900, 8vo, 700 pages (Masson et Cie.), Hayem has brought his previous book 
in a measure up to date, but the " Lemons " are very diffuse and wordy and 



488 



BIBLIOGRAPHY. 



contain but a small fraction of the original work for which Haycni's first hook 
was so notable. 

4. V. Limbeck: " Grundriss ein. klin. Pathologic des Bliites," Jena, 1896, 
8vo, 383 pages (Fischer). The second edition of this book, which appeared 
in February, 1896, is more than twice the size of the first edition (1892) — a 
fact illustrating the rapidity of the subject's growth. It is on the whole the 
best general text-book known to me, being equally full on all parts of the 
subject, including, for example, technique (which Grawitz omits) and of the 
cliemistr}" of the blood, which is at present the author's special interest and on 
which Hayem is meagre. The illustrations are poor and the type is trying to 
the eyes. The writer shows little personal experience with the morphology 
and micro-chemistry of the blood, and this is the weakest side of the book. A 
large part of the book is concerned with the physiology of the blood. 

5. Grawitz: "Klinische Pathologic des Blutes," Berlin, 1895, Svo, 333 
pages (Enslin). Issued in April, 1896. This book is largely devoted to the 
matter indicated hj the title and contains no account of blood technique, and 
only thirty pages on the normal anatomy and physiolog}' of the blood, while 
two hundred and seventy concern the blood in disease. The arrangement of 
the book is very clear and helpful. The author's main interests are in the 
estimation of the dried residue of the blood in various diseased conditions and 
in the bacteriology of the blood, so that the book is specially full on these 
topics. The illustrations are poor. Type and paper are excellent. 

6. Coles: " The Blood: How to Examine It," etc., London, 1898 (J. and A. 
Churchill), Svo. A clear and fairly complete account of the work of others 
upon the subject. Especially full on technique. 

These are the best text-books known to me on the whole subject. 
Taylor's masterly monograph, entitled " Studies in Leukaemia " and 
forming part of the volume of " Contributions from the AVilliam 
Pepper Laboratory of Clinical Medicine " (Philadelx^hia, 1900), 
contains within its one hundred and seventy-eight quarto pages not 
merely an unrivalled account of leukaemia but a great deal of im- 
portant matter on leucocytosis, anaemia, and most other haemato- 
logical to^Dics. It is by far the best study of leukaemia known to 
me in any language. 

Treatises on Special Portions of the Subject. 

1. Reinert's " Die Zahlung der Blutkorperchen, " Leipzig, 1891 (Vogel), 246 
pages, is an admirable account of the avoidable and unavoidable errors in 
blood examination, and the best methods of reducing error to a minimum. A 
number of careful examinations of the blood in health and in various diseases 
are also given ; and an outline of the scope of blood diagnosis closes the book. 

2. Turk's monograph on the "Condition of the Blood in Acute Infectious 
Disease " is an admirable resume of German and French literature on the sub- 
ject, together with a detailed study of fiftj^-two cases. Published at Wien 
and Leipzig, 1898 (Braumuller), 347 pagss, 8vo. 



BIBLIOGRAPHY. 



489 



3. Rieder's "Beitriige zur Kenntniss der Leukocytosis," Leipzig, 1892 
(Vogel), 220 pages, is an admirable work in all respects, although now consid- 
erably out of date. It shows, as very few of the foregoing treatises do, a 
practical acquaintance, on the author's part, with the details of blood mor- 
phology and microchemistry. A very large number of blood counts in many 
diseases are recorded. 

4. Lowitt's " Studien zur Physiol, und Pathol, des Blutes u. der Lymphe " 
(Jena, 1892 [Fisher] , 8vo, 138 pages) is mostly concerned with experiments on 
animals and intended to throw light on the theory of leucocytosis. The con- 
clusions of the book have not been generally adopted, though its facts have 
been mostly verified. 

5. Thayer and Hewetson's book, on the "Malarial Fevers of Baltimore," 
leaves nothing more to be desired in that direction. It is two hundred and 
fifteen pages long, published by the Johns Hopkins press of Baltimore in 1895. 
It contains a summary of the literature of the subject, an analysis of six hun- 
dred and sixteen new cases, and some admirable colored plates. It is a model 
of its kind in every respect, and an ideal for others to aim for. Essentially 
the same material is reorganized in Thayer's " Lectures on the Malarial Fevers, " 
New York, 1899, Appleton. 

6. Ehrlich's " Farbenanalytische Untersuchungen " (Berlin, 1891 [Hirsch- 
wald], 137 pages) contains nine short essays by Ehrlicli and three by his pu- 
pils. Considering the reputation of the writer they are at the present day 
rather disappointing reading, and contain little that is not better expressed 
elsewhere. 

7. Weiss's "Hsematologische Untersuchungen " (Wien, 1896. [Prochaska] 
112 pages, 8vo) contains many valuable studies on various points. 

Magazine Articles of Special Value. 

1. On Concentration and Dilution of the Blood — Oliver: Lancet, June 27, 
1896. 

2. On Leucocytosis — Goldschneider and Jacob : Zeit. f iir klin. Med. , 1894, 
vol. 25. Krebs: Inaug. Dissert., Berlin, 1893. Sadler: Fortschr. d. Med., 
Supplement-Heft, 1892. Also Klein, in Volkmann's Sammlung klinischer 
Vortrage, December, 1893, and of course Rieder and Tiirk above referred to. 

3. On Anaemia — Dunin: Volkmann's Sammlung klin. Vortrage, 1896, No. 
135. Romberg: Berlin, klin. Woch., June 28, 1897. 

4. Parasitic Ancemia — Schaumann : Zur Kenntniss der sog. Bothriocepha- 
lus Anamie, Berlin, 1892, 214 pages; and Askanazy: Zeitschr. f. klin. Med., 
1895, p. 492. Brown: Journal of Experimental Medicine, May, 1898 (Trichi- 
nosis). 

5. Leukaemia — Fraenkel: Deutsche med. Wochenschrift, 1895, p. 639, 
Fraenkel: 15th Congress f iir inn. Medicin, Wiesbaden, 1897. Benda: Ibidem. 
Dock : Moscow Internat. Congress, 1897. 

6. Pernicious Anaemia — Discussion by Birch- Hirschf eld, Ehrlich, Troje, 
and others, at the XI. Congress f. inner. Med. (Leipzig, 1892). 

7. Pneumonia — Billings: Bulletin of the Johns Hopkins Hospital, Novem- 
ber, 1894. Diphtheria— Billings: New York Medical Record, April 25, 1896. 



490 



BIBLIOGRAPHY. 



Typhoid — Thayer: Johns Hopkins Hospital Reports, vol. iv., No. 1. Engel: 
IStli Congress fur inn. Med., Wiesbaden, 1897. Exanthemata — Felsentlial: 
Arch. f. Kinderheilk., 1892, p. 78. Zappert: Zeitschr. f. klin. Med., 1893, 
No. 23. Smallpox— Pick: Arch. f. Dermatol, und Syph., 1893, p. 63. Sepsis 
— Roscher: Inaug. Dissert., Berlin, 1894. Cholera — Biernacki: Deutsche med. 
Wochenschr., 1895, No. 48. Diabetes — Bremer: Moscow Internat. Congress, 
1897. 

8. Syphilis— (a) Reiss: Arch. f. Dermat. und Syph., 1895, Hft. 1 and 2. 
(b) Justus: Virchow's Arch., 1895. 

9. Tuberculosis — (a) Dane : Boston Medical and Surgical Journal, May 28, 
1896. (b) Stein und Erbmann: Deutsche med. Wochenschrift, 1896, No. 56, 
p. 323. (c) Grawitz: Deutsche med. Wochenschr., 1893, No. 51. 

10. Malignant Disease — Taylor (International Medical Magazine, July, 
1897). (a) Sadler: Loc. cit. (b) Reinbach: Langenbeck's Archiv, 1893, No. 
46. (e) Strauer: Dissert., Greifswald, 1893. 

11. Bacteriology — Sittmann: Deutsclies Arch. f. klin. Med., vol. 53. 

12. Diseases of the Stomach (especially Cancer) — Schneyer : Zeitschrif t f . 
klin. Med., 1895, p. 475. Osterspey: Inaug. Diss., Berlin, 1892. 

13. Eosinophiles— Zappert : Zeitschr. f. klin. Med.. 1893, vol. 23. 

14. Haemoconien — Miiller: Wien. med. Presse, 1896, No. 36. 



INDEX. 



Abscess, 205, 239 

diagnostic value of blood in, 252 

felon, 251 

gum boil, 251 

of liver, 315 

of lung, 251 

of neck, 251 

of ovary, 251 

of parotid, 251 

of vulva, 251 

perinephritic, 251 

psoas, 251 

subpectoral, 251 

subphrenic, 251 

vaginal, 251 
Actinomycosis, 256 
Acute yellow atrophy of liver, 311 
Addison's disease, 354 
Adenitis, 176 
Alcoholism, 366 
Alkalinit}^ of blood, 49 
Altitude, effects on blood, 78 
Amoeboid movements, 53 
Anaemia, 80 

aplastic, 152 

infantum pseudoleukamica, 450 
of infancy, 447 
pernicious, 131 
primary, 81 

secondary or symptomatic, 83 
splenic, 185 
tropical, 81 

with dilated stomach, 300 

with ulcer of stomach, 293 
Aneurism, 326 
Antitoxin (diphtheria), 210 
Appendicitis, 240 

diagnosis of, 246 

fibrin in, 243 

Bacteriology of the blood, 47 

in pneumonia, 189 
Basedow's disease, 353 
Beri-beri, 257 
Bleeders, 8 • 
Blood destruction, 358 
Bronchitis, 205, 33^ 

acute, 338 



Bronchitis, chronic, 339 
Brownian movement, 11, 85 
Bubonic plague, 255, 467 
Burns, influence on blood, 361 

Caisson disease, 346 
Cancer, 370 

eosinophiles in, 392 

generalized, 390 

leucocytes in, 377 

myelocytes in, 392 

nucleated red cells in, 376 

of abdominal organs, 387 

of breast, 379, 390 

of gullet, 384 

of intestine, 386 

of kidney, 388, 390 

of lip, 390 

of liver, 385 

of mediastinum, 390 

of neck, 390 

of omentum, 387 

of ovary, 390 

of pancreas, 390 

of prostate, 390 

of skull, 390 

of stomach, 380 

of stomach, digestion leucocyte- 

sis in, 382 
of uterus, 389 
of vertebrae, 390 

position of tumor and its influ- 
ence, 377 

qualitative changes in blood, 375 

qualitative changes in leuco- 
cytes, 391 

regeneration of blood in, 374 
Cathartics, influence on blood, 301 
Charcot-Leyden crj^stals, 170 
Chlorosis, 153 

blood plates in, 158 

deformities in, 156 

diagnosis of, 159 

eosinophiles in, 158 

lymphocytes in, 158 

myelocytes in, 158 

neutrophiles in, 158 

red cells in, 154 



492 



INDEX. 



Chlorosis, specific gravity. 157 

volume of blood in. 153 

Avhite cells in, 157 
C'liola'mia. 312 
(']i(ilaiii!-itis, 314 
Chok-cvstitis, 205, 314 
Cholera. 226 

acidity of blood in. 226 

serinn reaction in, 466 
Chorea. 346 
Cirrhosis of liver. 307 
Coagulation in jaundice. 48 

in pernicious anaania. 49 

in purpura. 4S 

of l)lood. 65. 69 
Concentration of blood. 75 
Conjunctivitis, 205 
Constitutional diseases, 349 
Convulsions, effect of. 346 
Corpuscles, biconcavity. 52 

crenatiou. 52 

numlier of. 56-59 

red. effects of fatigue on, 58 

resistance, 49, 51 

white, 53 
Counting corpuscles. 12-27 

corpliscles (differential). 46 
Cretinism, 353 
Cyanosis, 190 
Cystitis, 205 

Degeneeatiox of corpuscles. 52, 191 
Diabetes, 349 
Diarrhoea, 9 

Digestion leucocytosis in cancer, 382 
Digestive organs, diseases of, 292 
Diplitheria, 210 
Distribution of blood. 72 
Dunham's hremocytometer, 23 
Duodenal ulcer, 297 
Dysenterv, 209 
Dyspepsia, 298 

ECHIXOCOCCUS cvst. 311 
Electric shock. 369 
Electricity, elfect on blood, 50 
Emphysema, 340 
Empyema. ^62 
Endocarditis. 316 
End 0 globular changes, 84 
Eosinophiles, 65, 18^, 193, 206 
Eosinophilia after tuberculin, 274 

compensatory. 117 

diagnostic value of, 118 

in aciue and chronic skin dis- 
eases, 115 

in ankylostomiasis, 116, 428, 432 

in asthma. 340 

in cancer, 116, 392 

in tibrinous pneumonia. 115 



Eosinophilia in hfi'matoma. 117 

in helminthiasis, 116 

in purpura, 117 

in scarlatina, 216 

in trichinosis. 116. 435 

medicinal. 117 

phvsiological. 115 

post-febrile, 116 
Epidemic dropsy, 256 
Erysipelas. 227 
Erythema nodosum. 209 

F-iX Ai. impaction. 247 
Fever, intluence of, 188, 198 
Fibrin, 54, 121, 198 
Filariasis, 417 
Furunculosis, 204 

Gall-stone colic, 247 
Gall stones. 312 
Gastric ulcer, 293-297 
Gastritis, acute and chronic, 298, 299 
corrosive. 301 

digestion leucocytosis in, 300 

in infancy, 449 

with hyperacidity, 300 
General paralysis, 346 
Glanders. 255' 
Gonorrhoea, 253 
Gout, 351 

Gowers' solution, 18 
Graves' disease. 353 
Grippe, 229 
Gumma of liver, 315 

HEMATOCRIT, 31 

Haemocvtolv-sis, 360 

Haemoglobin, 32. 120 

Haemoglobinamia, 360 

Hamoglobinometers, 32-37 

Haemophilia, 359 

Hayem"s solution. 27 

Heart, congenital disease of, 323 

diseases of, 316-323 
Heat exhaustion, 368 
Hemorrhage, 123. 202 

blood degeneration after, 123 

chronic, 127 
Hodgkin's disease, 179, 453 
Hydrtemia, 93 
Hydronephrosis, 176 
Hypochondriasis, 347 
Hysteria, 347 

IxTAXCY, anaemias of, 447 
blood in, 44.5-456 
chlorosis in^ 448 
hereditary syphilis in, 449 
leucocytosis in. 445 
leukaemia in, 456 



INDEX. 



493 



Infancy, lymphocytosis in, 445 

polj-cytlia^nia in, 445 

rickets in, 449 
Influenza, 209 

Intestinal parasites, 426, 440 
Intestine, disease of, 301 

obstruction of, 304 
lodophilia, 239 
Isotonic coefficient, 50 

Jaundice, catarrhal, 304 

coagulation in, 305 
Justus reaction in sj^philis, 288 

Kidneys, diseases of, 247, 327-337 
pyonephrosis, 337 
uraemia, 334 

Leprosy, 291 
Leucocytes, 53 

degenerated, 70 

eosinophilic (see Eosinophiles), 64 
in abscess, 239 
in smallpox, 219 
iodine reaction in, 239 
mononuclear neutrophilic, 65, 68, 
70 

normal percentages of, 67 

origin of, 67 

polymorphonuclear, 65 

"stimulation forms," 71 

transitional neutrophiles, 71 
Leucocytosis, absence of, 111 

after exercise, massage, and 
baths, 100 

cell changes in, 96, 110 

definition. 94 

diagnostic value of, 98 

digestive, 97 

experimental, 109 

intlammatory, 104 

in malignant disease, 108 

in new-born infants, 99 

in pneumonia, 191 

in pregnanc3^ 100 

in shock, 106 

pathological, 104 

phj^siological, 95 

post-liemorrhagic, 104 

post-partum, 100 

terminal, 103 

therapeutic, 109, 178, 192 

toxic, 107 
Leucopenia, 112, 185 
Leukaemia, 160-185 

remissions in, 170 
Lipoemia, 122 
Lymph^emia, 170 
Lymphatic leukaemia. 170 
Lymphocytes, 62 



Lymphoc3^tosis, 113 

in hereditary syphilis, 113 

in infancy, 113 

in pertussis, 113 

in splenic tumors, 114 

in thyroidism, 114 

Macrocytes, 83, 155 

Malaria, 176, 238, 404-416 
parasites of, 404 
pigmented parasites, 405 
segmenting parasites, 405 
typhoid, 208 

Malta fever, 255, 466 

Mast cells, 66, 169 

Megaloblasts, 88, 162, 190 

Melancemia, 122 

Meningitis, 209, 266-268, 282 
tuberculous, 282 

Mental diseases, 348 

Microblasts, 90 

Microcytes, 83 

Miiller's blood dust, 60 

Myelocytes, 68, 118, 165, 194, 347, 
*392, 399, 450 

Myeloid leuksemia, 161, 177 

Myxoedema. 351 

Necrobiosis of red cells, 83 
Nephritis, 327 

Nervous system, diseases of, 343-345 

Neuralgia, 246 

Neurasthenia, 347 

Neuritis, 343 

Newton's rings, 15 

Normoblasts, 87, 162, 190 

Nucleated red cells, 190, 376, 431 

Obesity, 349 

Oliver's instruments, 23, 27, 35 
Osteomalacia, 355 
Osteomyelitis, 251 
Otitis media, 205 

Pancreas, diseases of, 315 
Parasites, filarial, 417 

intestinal, 426 

malarial, 402 

of the blood, 402, 426 
Parotitis, 205 
Pericarditis, 205, 265, 285 

tuberculous, 285 
Periostitis, 205 
Peritonitis, 264 

tuberculous, 280 
Pernicious an£emia, 131 

anaemia, diagnosis of, 146 

anaemia, gross appearance of 
blood, 131 

anaemia, haemoglobin in, 136 



494 



INDEX. 



Pernicious anaemia in infancy, 452 
anaemia, nucleated red cells in, 
139 

anoemia, prognosis in, 149 

anaemia, red cells in. 132, 137 

ana:miia, remissions in, 144 

ana^mia. white cells in, 135, 142 

malaria (see Malaria) 
Phosphorus poisoninsr, 311 
Phthisis, 271, 273 
Pipettes, use and care of, 18 
Platelets, 53, 198 
Plethora. 74 
Pleurisv. purulent. 262 

serous. 2()4. 259 

tuberculous. 285 
Plumbism. 367 
Pneumonia. 176. J89. 204 

Ijacteriology of blood, 187 

broncho-, 1*97, 205 
Poikilocytosis, 83 
Poisoning, by ammonia, 365 

by antipyretics. 361, 363 

by arsenic. 366 

by carbolic acid, 366 

by carbonic oxide, 79, 363 

by ether, 365 

bv illuminatinar gas, 363 

by lead. 367 

bv opium. 365 

by phosphorus. 31 1, 363 

by potassium chlorate. 361 

bv ptomaiu'^. 365 

by pyrn-allic acid. 363 

by snake venom. 361 

bv lausv. 365 

effects on blood. 363 
Polychromatophilia. 86 
Polycythtemia, 72-74 
Preu'nancy. 247 
Purpura. 358 
Pus tulje. 24S 

Regenkeatiox of blood, 124 
Relapsing: fever. 257, 422 
Rheumat'ism. 221-226 
Rickets. 356. 449 
Rouleaux formati(jn, 51 

Sarcoma. 394-399 
Scarlatina. 215 
Seurvv. 359 
Septicemia. 230-237 



Serous membranes, diseases of. 259-. 
264 

Serum diagnosis, 458 

diagnosis of bubonic plague, 467 
diagnosis of cholera, 466 
diagno.sis of Malta fever, 466 
diagnosis of typhoid. 458 

Skin, diseases of, 442 

Slides, preparation of, 9, 41 

Smallpox, 217 

Snake poison, 361 

Solids of the blood. 50 

Specific gravity of blood, 39, 190, 198 

Splenectomy, i84 

Splenic anaemia. 185 
extract. 178 

myeloid leukaemia (see Leukae- 
mia) 

Staining blood films, 43, 64, 61 
Sunstroke. 21 
Syphilis, 286-290, 449 

Tetanus, 257 
Tetany, 346 

Thoma-Zeiss' instruments. 13, 15 

Thrombosis, 204 

Thyroid extract, effects of, 351 

Toisson's solution, 13 

Tonsillitis. 228 

Toxicitv of blood. 190. 200 

Trichinosis. 2o9. 434 

Tuberculosis, 269-2S6. 449 

acute miliary. 277 

fibrin in. 27o 

glandular, 2S5 

leucocytes in. 271 

of bone, 275 

of meninges, 282 

of pericardium, 285 

of peritoneum. 280 
Typhoid fever, 197-207 

fever, serimi reaction in, 458 

Urethritis. 205 
Uric acid in blood, 351 

Vaccinia. 220 
Varicella. 221 
Variola, 219 

Yellow fever, 253 

Zappert"s countins chamber, 16 



